Complement C4b: The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).Complement C3: A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.Complement Inactivator Proteins: Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.Complement C4: A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.Complement C4b-Binding Protein: A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).Light-Harvesting Protein Complexes: Complexes containing CHLOROPHYLL and other photosensitive molecules. They serve to capture energy in the form of PHOTONS and are generally found as components of the PHOTOSYSTEM I PROTEIN COMPLEX or the PHOTOSYSTEM II PROTEIN COMPLEX.Complement C4a: The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.Protein S: The vitamin K-dependent cofactor of activated PROTEIN C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S; (PROTEIN S DEFICIENCY); can lead to recurrent venous and arterial thrombosis.Complement C3b: The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.Complement C3a: The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.Complement C1q: A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.Complement Activation: The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.Complement C5a: The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.Photosynthetic Reaction Center Complex Proteins: Protein complexes that take part in the process of PHOTOSYNTHESIS. They are located within the THYLAKOID MEMBRANES of plant CHLOROPLASTS and a variety of structures in more primitive organisms. There are two major complexes involved in the photosynthetic process called PHOTOSYSTEM I and PHOTOSYSTEM II.Complement C5: C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Complement C6: A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms.Complement C3c: A 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.Receptors, Complement: Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.Complement C3d: A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).Complement C2: A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).Photosystem II Protein Complex: A large multisubunit protein complex found in the THYLAKOID MEMBRANE. It uses light energy derived from LIGHT-HARVESTING PROTEIN COMPLEXES to catalyze the splitting of WATER into DIOXYGEN and of reducing equivalents of HYDROGEN.Complement C9: A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Complement C1s: A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).Complement C3-C5 Convertases: Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.Complement Membrane Attack Complex: A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Complement C1r: A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.Complement Factor B: A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Complement Pathway, Alternative: Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment CHLOROPHYLL, which is associated with the membrane of THYLAKOIDS. Chloroplasts occur in cells of leaves and young stems of plants. They are also found in some forms of PHYTOPLANKTON such as HAPTOPHYTA; DINOFLAGELLATES; DIATOMS; and CRYPTOPHYTA.Receptors, Complement 3b: Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Complement C7: A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.Complement Pathway, Classical: Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Complement C8: A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.Complement Factor H: An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Complement C1: The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.Light: That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.Complement Factor I: A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.Complement C5b: The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.Complement C2a: The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).Plants: Multicellular, eukaryotic life forms of kingdom Plantae (sensu lato), comprising the VIRIDIPLANTAE; RHODOPHYTA; and GLAUCOPHYTA; all of which acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations.Receptor, Anaphylatoxin C5a: A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Complement Activating Enzymes: Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.Poly(A)-Binding Proteins: Proteins that bind to the 3' polyadenylated region of MRNA. When complexed with RNA the proteins serve an array of functions such as stabilizing the 3' end of RNA, promoting poly(A) synthesis and stimulating mRNA translation.Complement Inactivating Agents: Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.Complement Hemolytic Activity Assay: A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.Complement C1 Inactivator Proteins: Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.Cytochalasin B: A cytotoxic member of the CYTOCHALASINS.Receptors, Complement 3d: Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.Anaphylatoxins: Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Complement C3b Inactivator Proteins: Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.Complement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Complement Factor D: A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cell Line: Established cell cultures that have the potential to propagate indefinitely.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Antigens, CD55: GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.Antigens, CD46: A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.Tacrolimus Binding Proteins: A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-Complement C3-C5 Convertases, Classical Pathway: Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.Complement C2b: The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Antigens, CD59: Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)Recombinant Proteins: Proteins prepared by recombinant DNA technology.Poly(A)-Binding Protein I: A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Cobra Venoms: Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.Kinetics: The rate dynamics in chemical or physical systems.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Insulin-Like Growth Factor Binding Proteins: A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Steroid 21-Hydroxylase: An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Complement C3-C5 Convertases, Alternative Pathway: Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.Complement C1 Inhibitor Protein: An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.Monosaccharide Transport Proteins: A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES.Hemolysis: The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.Complement C3 Convertase, Alternative Pathway: A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.Complement C5 Convertase, Classical Pathway: A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Complement C3 Convertase, Classical Pathway: A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Molecular Weight: The sum of the weight of all the atoms in a molecule.3-O-Methylglucose: A non-metabolizable glucose analogue that is not phosphorylated by hexokinase. 3-O-Methylglucose is used as a marker to assess glucose transport by evaluating its uptake within various cells and organ systems. (J Neurochem 1993;60(4):1498-504)Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Fatty Acid-Binding Proteins: Intracellular proteins that reversibly bind hydrophobic ligands including: saturated and unsaturated FATTY ACIDS; EICOSANOIDS; and RETINOIDS. They are considered a highly conserved and ubiquitously expressed family of proteins that may play a role in the metabolism of LIPIDS.Opsonin Proteins: Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Mice, Inbred C57BLMembrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Complement C5 Convertase, Alternative Pathway: A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.S100 Calcium Binding Protein beta Subunit: A calcium-binding protein that is 92 AA long, contains 2 EF-hand domains, and is concentrated mainly in GLIAL CELLS. Elevation of S100B levels in brain tissue correlates with a role in neurological disorders.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Poly(A)-Binding Protein II: A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Bacterial Proteins: Proteins found in any species of bacterium.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Complement Pathway, Mannose-Binding Lectin: Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)CapZ Actin Capping Protein: An actin capping protein that binds to the barbed-ends of ACTIN filaments. It is a heterodimer consisting of an alpha and a beta subunit. It regulates actin assembly by stabilizing actin oligomers for elongation. In SKELETAL MUSCLE, CapZ is localized to the Z-disk.Properdin: A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Complement C5a, des-Arginine: A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).MethylglucosidesSignal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Insulin-Like Growth Factor Binding Protein 3: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Periplasmic Binding Proteins: Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Macrophage-1 Antigen: An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Tacrolimus Binding Protein 1A: A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.Latent TGF-beta Binding Proteins: A family of secreted multidomain proteins that were originally identified by their association with the latent form of TRANSFORMING GROWTH FACTORS. They interact with a variety of EXTRACELLULAR MATRIX PROTEINS and may play a role in the regulation of TGB-beta bioavailability.Serum: The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Framycetin: A component of NEOMYCIN that is produced by Streptomyces fradiae. On hydrolysis it yields neamine and neobiosamine B. (From Merck Index, 11th ed)Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Insulin-Like Growth Factor Binding Protein 2: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.S100 Proteins: A family of highly acidic calcium-binding proteins found in large concentration in the brain and believed to be glial in origin. They are also found in other organs in the body. They have in common the EF-hand motif (EF HAND MOTIFS) found on a number of calcium binding proteins. The name of this family derives from the property of being soluble in a 100% saturated ammonium sulfate solution.Glomerulonephritis, Membranoproliferative: Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)TATA-Box Binding Protein: A general transcription factor that plays a major role in the activation of eukaryotic genes transcribed by RNA POLYMERASES. It binds specifically to the TATA BOX promoter element, which lies close to the position of transcription initiation in RNA transcribed by RNA POLYMERASE II. Although considered a principal component of TRANSCRIPTION FACTOR TFIID it also takes part in general transcription factor complexes involved in RNA POLYMERASE I and RNA POLYMERASE III transcription.Schistosoma: A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Insulin-Like Growth Factor Binding Protein 1: One of the six homologous proteins that specifically bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions. The function of this protein is not completely defined. However, several studies demonstrate that it inhibits IGF binding to cell surface receptors and thereby inhibits IGF-mediated mitogenic and cell metabolic actions. (Proc Soc Exp Biol Med 1993;204(1):4-29)Glomerulonephritis: Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Cyclic AMP Response Element-Binding Protein: A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Arteriolosclerosis: Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Mice, Inbred BALB CPhenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Retinol-Binding Proteins: Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a non-covalently-bound ligand.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.S100 Calcium Binding Protein G: A calbindin protein found in many mammalian tissues, including the UTERUS, PLACENTA, BONE, PITUITARY GLAND, and KIDNEYS. In intestinal ENTEROCYTES it mediates intracellular calcium transport from apical to basolateral membranes via calcium binding at two EF-HAND MOTIFS. Expression is regulated in some tissues by VITAMIN D.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.CREB-Binding Protein: A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Vitamin D-Binding Protein: An alpha-globulin found in the plasma of man and other vertebrates. It is apparently synthesized in the liver and carries vitamin D and its metabolites through the circulation and mediates the response of tissue. It is also known as group-specific component (Gc). Gc subtypes are used to determine specific phenotypes and gene frequencies. These data are employed in the classification of population groups, paternity investigations, and in forensic medicine.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.CCAAT-Enhancer-Binding Proteins: A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Proto-Oncogene Proteins c-rel: Cellular DNA-binding proteins encoded by the rel gene (GENES, REL). They are expressed predominately in hematopoietic cells and may play a role in lymphocyte differentiation. Rel frequently combines with other related proteins (NF-KAPPA B, I-kappa B, relA) to form heterodimers that regulate transcription. Rearrangement or overexpression of c-rel can cause tumorigenesis.

Enhancement of lectin pathway haemolysis by immunoglobulins. (1/74)

We recently reported that indicator sheep erythrocytes (E) coated with mannan and sensitized with mannan-binding lectin (MBL) (E-M-MBL) are lysed by human serum in the absence of calcium via the lectin pathway of complement activation by a process which requires alternative pathway amplification and is associated with increased binding of and control by complement regulatory proteins C4 bp and factor H. In the present study, we investigated the effect of immunoglobulin (Ig) on this haemolysis. Co-sensitization of indicator E with anti-E haemolysin led to threefold enhancement of lectin pathway haemolysis in the absence of calcium, associated with increased binding of C3 and C5. Lysis was enhanced approximately twofold when E-M-MBL were chemically or immunologically coated with IgM or IgA, and fourfold when coated with IgG, prior to lysis in human serum-Mg-ethyleneglycol tetraacetic acid. The presence of haemolysin did not reduce the binding or inhibitory activity of C4 bp, and the enhancing activity of haemolysin was retained in serum depleted of C4 bp. By contrast, binding of factor H was greatly reduced in the presence of haemolysin, which had no enhancing effect in serum depleted of factor H. These experiments demonstrate the ability of IgG, IgM and IgA to enhance lectin pathway cytolysis, and that this enhancement occurs by neutralization of the inhibitory activity of factor H. Immunoglobulin enhancement of lectin pathway cytolysis represents another interaction between the innate and adaptive systems of immunity.  (+info)

Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins. (2/74)

Mannan-binding lectin (MBL) is an acute phase protein which activates the classical complement pathway at the level of C4 and C2 via two novel serine proteases homologous to C1r and C1s. We recently reported that haemolysis via this lectin pathway requires alternative pathway amplification. The present experiments sought to establish the basis for this requirement, and hence focused on the activity and regulation of the C3 convertases. Complement activation was normalized between the lectin and classical pathways such that identical amounts of bound C4 and of haemolytically active C4,2 sites were present on the indicator cells. Under these conditions, there was markedly less haemolysis, associated with markedly less C3 and C5 deposited, via the lectin pathway than via the classical pathway, particularly when alternative pathway recruitment was blocked by depletion of factor D. Lectin pathway activation was associated with enhanced binding in the presence of MBL of complement control proteins C4bp and factor H to C4b and C3b, respectively, with decreased stability of the C3-converting enzyme C4b,2a attributable to C4bp. Immunodepletion of C4bp and/or factor H increased lectin pathway haemolysis and allowed lysis to occur in absence of the alternative pathway. Thus, the lectin pathway of humans is particularly susceptible to the regulatory effects of C4bp and factor H, due at least in part to MBL enhancement of C4bp binding to C4b and factor H binding to C3b.  (+info)

Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis. (3/74)

Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor C4b-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C4bp, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of C4b by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation.  (+info)

C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation. (4/74)

After cell death, via apoptosis or necrosis, the uptake of dead cells by neighboring cells or phagocytes prevents the release of intracellular content. An array of molecules, including initiation molecules of the complement system, are involved in marking dead cells for uptake. After binding of these molecules, complement activation takes place, which when uncontrolled might result in a proinflammatory state. In the current study we demonstrate that complement inhibitor, C4b-binding protein (C4BP), binds strongly to necrotic cells, irrespective of the cell type used or the method of induction. After binding of the C4BP-protein S (PS) complex to necrotic cells via PS-phosphatidylserine and C4BP-DNA interactions, C4BP-PS inhibits complement activation on these cells. C4BP binds DNA via a patch of positively charged amino acids, mainly on the second complement control domain of the C4BP alpha-chain (affinity constant: 190 nM). Furthermore, C4BP limits DNA release from necrotic cells and inhibits DNA-mediated complement activation in solution. The C4BP-necrotic cell interaction also occurs in vivo as necrotic areas of arteriosclerotic plaques and of various cancers stain strongly positive for C4BP. This study describes a novel mechanism in which C4BP limits the inflammatory potential of necrotic cells.  (+info)

In vivo clearance of human protein S in a mouse model: influence of C4b-binding protein and the Heerlen polymorphism. (5/74)

OBJECTIVE: To explore the effect of the Heerlen polymorphism and C4b-binding protein (C4BP) on protein S catabolism in vitro and in vivo. METHODS AND RESULTS: Radiolabeled protein S was efficiently bound and intracellularly degraded by THP-1 macrophages, and both processes were strongly reduced in the presence of the protein S-carrier protein C4BP. To test whether C4BP displays a similar protective effect in vivo, survival experiments were performed in mice. In the absence of C4BP, radiolabeled human protein S disappeared in a biphasic manner (mean residence time [MRT] 2 hours). However, the presence of C4BP resulted in a 4-fold prolonged survival of protein S (MRT 8 hours; P<0.0001). We also applied this experimental model to recombinant protein S-Heerlen, a naturally occurring variant that contains a Ser460Pro substitution. These clearance experiments revealed a strongly decreased survival of recombinant protein S-S460P (MRT 0.6 hours; P=0.021), which could be compensated partially by C4BP (MRT 1.4 hours; P=0.012 compared with protein S-S460P). CONCLUSIONS: Protein S-S460P has a reduced survival in vivo, which may explain the low levels of free protein S in individuals carrying this polymorphism. Furthermore, C4BP prevents premature clearance of protein S and uses this ability to compensate the increased clearance of protein S-S460P.  (+info)

Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection. (6/74)

Neisseria gonorrhoeae is the causative agent of gonorrhea, a disease that is restricted to humans. Complement forms a key arm of the innate immune system that combats gonococcal infections. N. gonorrhoeae uses its outer membrane porin (Por) molecules to bind the classical pathway of complement down-regulatory protein C4b-binding protein (C4bp) to evade killing by human complement. Strains of N. gonorrhoeae that resisted killing by human serum complement were killed by serum from rodent, lagomorph, and primate species, which cannot be readily infected experimentally with this organism and whose C4bp molecules did not bind to N. gonorrhoeae. In contrast, we found that Yersinia pestis, an organism that can infect virtually all mammals, bound species-specific C4bp and uniformly resisted serum complement-mediated killing by these species. Serum resistance of gonococci was restored in these sera by human C4bp. An exception was serotype Por1B-bearing gonococcal strains that previously had been used successfully in a chimpanzee model of gonorrhea that simulates human disease. Por1B gonococci bound chimpanzee C4bp and resisted killing by chimpanzee serum, providing insight into the host restriction of gonorrhea and addressing why Por1B strains, but not Por1A strains, have been successful in experimental chimpanzee infection. Our findings may lead to the development of better animal models for gonorrhea and may also have implications in the choice of complement sources to evaluate neisserial vaccine candidates.  (+info)

Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor. (7/74)

Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation within C4BP. We thus provide a detailed picture of an interaction whereby a pathogen evades complement.  (+info)

Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation. (8/74)

Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood-brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA+ E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA- E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA+ E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum.  (+info)

article{5be1f4a6-d9f6-43e4-84be-f1c903a8b6fe, abstract = {C4b-binding protein (C4BP), an important inhibitor of complement activation, has a unique spider-like shape. It is composed of six to seven identical alpha-chains with or without a single beta-chain, the chains being linked by disulfide bridges in their C-terminal parts. To elucidate the structural requirements for the assembly of the alpha-chains, recombinant C4BP was expressed in HEK 293 cells. The expressed C4BP was found to contain six disulfide-linked alpha-chains. Pulse-chase analysis demonstrated that the recombinant C4BP was rapidly synthesized in the cells and the polymerized C4BP appeared in the medium after 40 min. The alpha-chains were polymerized in the endoplasmic reticulum (ER) already after 5 min chase. The polymerization process was unaffected by blockage of the transport from the ER to the Golgi mediated by brefeldin A or low temperature (10 degrees C). The C-terminal part of the alpha-chain (57 amino acids), containing ...
La nostra investigació està dedicada a lestudi dels mecanismes moleculars de la mort i la proliferació cel·lular, ja que aquests estan involucrats en el desenvolupament de diferents patologies humanes.. ...
The complement inhibitor C4b-binding protein (C4BP) prevents necrotic cells from spilling their pro-inflammatory guts, according to a study on page 1937. Trouw and colleagues now show that C4BP and its binding partner, anticoagulant protein S (PS), cooperate to grab onto necrotic cells and to inhibit the release of cellular DNA.. C4BP short-circuits the complement cascade by binding to the activated complement components C3b and C4b and presenting them to the proteolytic complement inhibitor Factor I for degradation. This inhibitory capacity of C4BP can be coopted by bacterial pathogens, which coat themselves with this protein to avoid complement-mediated destruction by phagocytic cells.. This group recently identified a role for the C4BP-PS complex: it binds to apoptotic cells through the phosphatidylserine-binding domain of PS. This association could prevent the deposition and activation of complement on the surface of the apoptotic cells, allowing the dying cells to be removed without ...
2A55: Human C4b-binding Protein, Structural Basis for Interaction with Streptococcal M Protein, a Major Bacterial Virulence Factor
Lipooligosaccharide (LOS) heptose (Hep) glycan substitutions influence gonococcal serum resistance. Several gonococcal strains bind the classical complement pathway inhibitor, C4b-binding protein (C4BP), via their porin (Por) molecule to escape complement-dependent killing by normal human serum (NHS). We show that the proximal glucose (Glc) on HepI is required for C4BP binding to Por1B-bearing gonococcal strains MS11 and 1291 but not to FA19 (Por1A). The presence of only the proximal Glc on HepI (lgtE mutant) permitted maximal C4BP binding to MS11 but not to 1291. Replacing 1291 lgtE Por with MS11 Por increased C4BP binding to levels that paralleled MS11 lgtE, suggesting that replacement of the Por1B molecule dictated the effects of HepI glycans on C4BP binding. The remainder of the strain background did not affect C4BP binding; replacing the Por of strain F62 with MS11 Por (F62 PorMS11) and truncating HepI mirrored the findings in the MS11 background. C4BP binding correlated with resistance to killing
Purpose:: A founder mutation in the C1QTNF5 short-chain collagen gene results in late-onset retinal macular degeneration (L-ORMD), which resembles age-related macular degeneration (AMD). The Y402H and other variants in the complement factor H (CFH) gene increase the risk of AMD. The aim was to investigate a possible interaction between C1QTNF5 and CFH. Methods:: Full length C1QTNF5 was expressed in a mammalian expression system, while its gC1q domain was expressed in a bacterial expression system. Both proteins were purified using Ni-NTA super-flow columns. Full length CFH was purified from human plasma. Recombinant segments of CFH, consisting of complement control protein domains 6-8 (CCP6-8), containing either 402Y or 402H alleles, were expressed in bacteria. The interaction between C1QTNF5, CFH and heparin were examined using binding assays and surface plasmon resonance (Biacore). Results:: C1QTNF5 was found to interact in a dose-dependent manner both with purified human CFH and with CCP6-8 ...
The aim of this study was to characterize the mechanisms by which C4b and streptococcal M proteins interact with C4BP. Furthermore, we wanted to identify a key recognition area in the C4BP α-chain involved in the binding of these ligands. To address this question, we used nine C4BP mutants and compared the ability of these molecules to interact with C4b and with the M proteins Arp4 and Sir22. Effects of NaCl and mAbs were also tested, and the experimental results were then evaluated in conjunction with structural analysis of a recently reported 3D model structure of human (8) and mouse C4BP. Taken together, our data show that the key binding region for C4b overlaps with the surface interacting with Arp4/Sir22 and is located on CCP1 and CCP2. However, the recognition areas are not identical and the molecular mechanisms involved in these two processes differ.. Previously published data from our group (10) together with the present results show that Arg39, Lys63, Arg64, and His67 are crucial for ...
Natural antibodies, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neo-antigenic determinants on apoptotic thymocytes is dominated by antibodies to oxidation-associated antigens, phosphorylcholine (PC), a head group that becomes exposed during programmed-cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive-oxidation species. While natural antibodies to apoptotic cells in naïve adult mice were dominated by PC and MDA specificities, the amounts of these antibodies were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA antibodies was affected by VH gene inheritance. Antibody interactions with apoptotic-cells also mediated the recruitment of C1q, which alone can promote apoptotic-cell
article{b6c22ab7-8314-43e4-a60f-8c80bb2fb02a, author = {Blom, Anna and Kask, Lena and Ramesh, Bala and Hillarp, Andreas}, issn = {0003-9861}, language = {eng}, number = {2}, pages = {108--118}, publisher = {Academic Press}, series = {Archives of Biochemistry and Biophysics}, title = {Effects of zinc on factor I cofactor activity of C4b-binding protein and factor H.}, url = {http://dx.doi.org/10.1016/j.abb.2003.08.018}, volume = {418}, year = {2003 ...
TY - JOUR. T1 - Structure and Function Characterization of the a1a2 Motifs of Streptococcus pyogenes M Protein in Human Plasminogen Binding. AU - Quek, Adam J.H.. AU - Mazzitelli, Blake A.. AU - Wu, Guojie. AU - Leung, Eleanor W.W.. AU - Caradoc-Davies, Tom T.. AU - Lloyd, Gordon J.. AU - Jeevarajah, Devadharshini. AU - Conroy, Paul J.. AU - Sanderson-Smith, Martina. AU - Yuan, Yue. AU - Ayinuola, Yetunde A.. AU - Castellino, Francis J.. AU - Whisstock, James C.. AU - Law, Ruby H.P.. PY - 2019/9/6. Y1 - 2019/9/6. N2 - Plasminogen (Plg)-binding M protein (PAM) is a group A streptococcal cell surface receptor that is crucial for bacterial virulence. Previous studies revealed that, by binding to the kringle 2 (KR2) domain of host Plg, the pathogen attains a proteolytic microenvironment on the cell surface that facilitates its dissemination from the primary infection site. Each of the PAM molecules in their dimeric assembly consists of two Plg binding motifs (called the a1 and a2 repeats). To date, ...
Protein therapeutics suffer from low oral bioavailability, mainly due to poor membrane permeability and digestion by gastrointestinal proteases. To improve proteolytic stability, intramolecular thioether crosslinks were introduced into a three-helix affibody molecule binding the human epidermal growth factor receptor (EGFR). Solid-phase peptide synthesis was used to produce an unmodified control protein domain and three different crosslinked protein domain variants: one with a thioether crosslink between the N-terminal lysine residue and a cysteine residue in the second loop region (denoted K4), a second with a crosslink between the C-terminal lysine residue and a cysteine residue in the first loop region (denoted K58), and a third with crosslinks in both positions (denoted K4K58). Circular dichroism (CD) and surface-plasmon-resonance-based (SPR-based) biosensor studies of the protein domains showed that the three-helix structure and high-affinity binding to EGFR were preserved in the ...
We describe a highly efficient two-step single-cell reverse transcriptase-polymerase chain reaction technique for analyzing gene expression at the single-cell level. Good reproducibility and a linear dose response indicated that the technique has high specificity and sensitivity for detection and quantification of rare RNA. Actin could be used as an internal standard. The expression of message for Rubisco small subunit (RbcS), chlorophyll a/b-binding protein (Cab), sucrose (Suc):fructan-6-fructosyl transferase (6-SFT), and Actin were measured in individual photosynthetic cells of the barley (Hordeum vulgare) leaf. Only Actin was found in the non-photosynthetic epidermal cells. Cab, RbcS, and 6-SFT genes were expressed at a low level in mesophyll and parenchymatous bundle sheath (BS) cells when sampled from plants held in dark for 40 h. Expression increased considerably after illumination. The amount of 6-SFT, Cab, and RbcS transcript increased more in mesophyll cells than in the parenchymatous ...
A Novel Protocol Allowing Oral Delivery of a Protein Complement Inhibitor that Subsequently Targets to Inflamed Colon Mucosa and Ameliorates Murine Colitis. Elvington, M; Blichmann, P; Qiao, F; Scheiber, M; Wadsworth, C; et al. A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis. Clinical and Experimental Immunology 177.2 (Aug 2014): 500-508. While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of ...
Graduate School of Biotechnology and Ginseng Bank, College of Life Science, Kyung Hee University, Yongin 446-701, Korea, dcyang [at] khu [dot] ac [dot] kr ...
human p50B-p97 protein: amino acid sequence given in first source; forms heteromeric kappa B-binding complexes with RelB; lacks phosphorylation site for protein kinase A, found in all other Rel-related proteins; We refer to the kappa B-binding, truncated protein as p50B by analogy with p50-NF-kappa B and to the full-length protein as p97
Xenozoonosis, also known as zoonosis or xenosis, is the transmission of infectious agents between species via xenograft. Animal to human infection is normally rare, but has occurred in the past. An example of such is the avian influenza, when an influenza A virus was passed from birds to humans.[33] Xenotransplantation may increase the chance of disease transmission for 3 reasons: (1) implantation breaches the physical barrier that normally helps to prevent disease transmission, (2) the recipient of the transplant will be severely immunosuppressed, and (3) human complement regulators (CD46, CD55, and CD59) expressed in transgenic pigs have been shown to serve as virus receptors, and may also help to protect viruses from attack by the complement system.[34] Examples of viruses carried by pigs include porcine herpesvirus, rotavirus, parvovirus, and circovirus. Porcine herpesviruses and rotaviruses can be eliminated from the donor pool by screening, however others (such as parvovirus and ...
Analysis of TNF-α-induced p65 nuclear entry, phosphorylation (Ser 536), promoter activity and IκBα degradation during DMF treatment. a Nuclear p65 translocat
Serum stimulation promotes p65 translocation into the nucleus as well as IκBα degradation. (A) p65-dsRed (red staining) and IκBα-EGFP (green staining) were
AMYNDAS is developing a novel peptidic complement inhibitor AMY-101, based on the third-generation compstatin analogue Cp40. AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the central functional hub that controls the upstream activation/amplification and downstream effector functions of complement. By binding to C3, AMY-101 inhibits the cleavage of native C3 to its active fragments C3a and C3b. As a consequence, the deposition of C3b, amplification via the alternative pathway and all downstream complement responses are prevented. AMY-101 is being developed to treat complement-mediated diseases, which are largely driven by aberrant C3 activation.. This first-in-human study of the C3-targeting complement inhibitor AMY-101 investigates the safety and PK/PD profile of AMY-101 in healthy male volunteers after Single Ascending Dose (SAD) and Multiple Doses (MD) using subcutaneous (SQ) or intravenous (IV) administration. The ...
NEW HAVEN, Conn.--(BUSINESS WIRE)--Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) announced today that the pivotal Phase 3 study of ALXN1210, the Companys investigational long-acting C5 complement inhibitor, demonstrated non-inferiority to Soliris® (eculizumab) in complement inhibitor treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) based on the co-primary endpoints of transfusion avoidance and normalization of lactate dehydrogenase (LDH) levels, a direct marker of complement-mediated hemolysis in PNH.
Mark, L, Spiller, OB, Okroj, M, Chanas, S, Aitken, JA, Wong, SW, Damania, B, Blom, AM and Blackbourn, DJ (2007) Molecular characterization of the rhesus rhadinovirus (RRV) ORF4 gene and the RRV complement control protein it encodes ...
Protein S is a vitamin K dependent cofactor for the anticoagulant activity of activated protein C (APC). Two forms of protein S are present in plasma : free protein S (40%) and protein S linked to the C4b-binding protein (60%). Only the free form has functional cofactor activity. Protein S deficiency may be hereditary or acquired - as in normal pregnancy. It has been associated with a high risk of developing venous thromboembolism especially in young people. As only the free form of Protein S has the cofactor activity it is only this form that is measured. Measurement of Protein S in pregnancy is rarely useful.. ...
Department of Biological Sciences, Texas Tech University, Lubbock 79409, USA. [email protected] The function of Lhca4, a gene encoding the photosystem 1 type IV chlorophyll a/b-binding protein complex in Arabidopsis, was investigated using antisense technology. Lhca4 protein was reduced in a number of mutant lines and abolished in one. The inhibition of protein was not correlated with the inhibition of mRNA. No depletion of Lhca1 was observed, but the low-temperature fluorescence emission spectrum was drastically altered in the mutants. The emission maximum was blue-shifted by 6 nm, showing that chlorophyll molecules bound to Lhca4 are responsible for most of the long-wavelength fluorescence emission. Some mutants also showed an unexplainable delay in flowering time and an increase in seed weight.. MeSH Terms ...
Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments ...
There is a growing awareness that complement plays an integral role in human physiology and disease, with an expanding list of pathologies that are linked to
SWISS-MODEL Repository entry for A8Y7N7 (VKTC4_DABSI), Kunitz-type serine protease inhibitor C4. Daboia siamensis (Eastern Russels viper) (Daboia russelii siamensis)
M2 Ethyl methanesulfonate (EMS) mutagenized Ler seeds were purchased from Lehle Seeds and examined under a dissecting microscope for the absence of giant cells in the sepal.. The dek1-4 mutation isolated contains a C to T change at base 6316 of the CDS, which causes a single amino acid substitution of a cysteine for conserved arginine 2106 in domain III of the calpain protease (supplementary material Fig. S2A) (Sorimachi and Suzuki, 2001). The dek1-4 allele fails to complement the reference dek1-3 (SAIL_384_G07) allele (data not shown), establishing that the absence of giant cells is due to the mutation in the DEK1 gene.. The dek1-4 mutation can be PCR genotyped by amplifying with oAR448 (5′-TGTTGGTGGAACAGACTATGTGAATTCA-3′) and oAR449 (5′-TGAAGACTGAAAGGACAAAAGGTGC-3′) with a 60°C annealing temperature followed by digesting the product with BsaAI to produce a 108 bp wild-type product or a 137 bp mutant product.. The atml1-2 allele isolated in this mutant screen contains a C to T change ...
The SCOP classification for the Complement control module/SCR domain family. Additional information, provided for both this family and the superfamily it belongs to, includes SUPERFAMILY links to genome assignments, alignments, domain combinations, taxonomic visualisation and hidden Markov model information.
Transcription of the surface-associated virulence factors of the group A streptococcus (GAS) Streptococcus pyogenes, M protein (emm) and the C5a peptidase (scpA), is activated by a protein called Mga (formerly Mry or VirR). To determine whether Mga binds directly to the promoters of the genes it regulates, a protein resulting from the fusion of Mga to the C-terminal end of maltose-binding protein was purified from Escherichia coli. Specific binding to the promoter regions of the scpA and emm alleles of the type M6 GAS strain JRS4 was demonstrated by electrophoresis of the DNA-protein complex. Competition studies showed that the region upstream of scpA bound MBP-Mga with a slightly higher affinity than did the region upstream of emm. DNase I protection experiments identified a single 45-bp binding site immediately upstream of and overlapping the -35 region of both promoters. Sequences homologous to the protected regions were found in the promoters of many emm, scp, and emm-like genes from strains ...
Transcription of the surface-associated virulence factors of the group A streptococcus (GAS) Streptococcus pyogenes, M protein (emm) and the C5a peptidase (scpA), is activated by a protein called Mga (formerly Mry or VirR). To determine whether Mga binds directly to the promoters of the genes it regulates, a protein resulting from the fusion of Mga to the C-terminal end of maltose-binding protein was purified from Escherichia coli. Specific binding to the promoter regions of the scpA and emm alleles of the type M6 GAS strain JRS4 was demonstrated by electrophoresis of the DNA-protein complex. Competition studies showed that the region upstream of scpA bound MBP-Mga with a slightly higher affinity than did the region upstream of emm. DNase I protection experiments identified a single 45-bp binding site immediately upstream of and overlapping the -35 region of both promoters. Sequences homologous to the protected regions were found in the promoters of many emm, scp, and emm-like genes from strains ...
HAE is an autosomal-dominant disorder characterized by recurrent nonpruritic edema of the skin and submucosal tissues.1,2,4-6 The prevalence of HAE ranges from 1 in 10,000 to 1 in 50,000 persons in the United States.4,7 Prevalence is not affected by sex or ethnicity; however, women may have more severe disease.1,4,7 A family history is present in approximately 75% of cases, indicating genetic inheritance; however, 25% of cases are thought to be due to a spontaneous mutation (i.e, a family history is absent).7 Patients often experience disease onset and a swelling episode during childhood, with an increase in severity during puberty.4,5,7,8 The frequency of attacks, which varies between patients, may be weekly or yearly.8. HAE is a congenital quantitative or functional deficiency of C1 esterase inhibitor (C1-INH); it is not associated with a hypersensitivity to foods or other allergens.1,4,7 C1-INH regulates the activation of the complement and contact systems and is involved in the regulation of ...
The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity ...
"Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein". FEBS Letters. 271 (1-2): 131-6. ... Complement C4-A is a protein that in humans is encoded by the C4A gene. This gene encodes the acidic form of complement factor ... "Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity". The ... The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma ...
... duttonii acquire complement regulators C4b-binding protein and factor H". Infection and Immunity. 74 (7): 4157-63. doi:10.1128/ ... It is notable for its ability to alter the proteins expressed on its surface, which causes the "relapsing" characteristic of ...
... they bind complement factors (C3b, C4b, factor H, and C4bp (complement factor 4b-binding protein)). Cooperation with pili for ... Factor H binding protein (fHbp) that is exhibited in N. meningitidis and some commensal species is the main inhibitor of the ... Factor H binding protein is key to the pathogenesis of N. meningitidis, and is, therefore, important as a potential vaccine ... Two encode proteins involved in pathogenicity. The third island only codes for hypothetical proteins. They also found more ...
... a free form and a complex form bound to complement protein C4b-binding protein (C4BP). In humans, protein S is encoded by the ... Dahlbäck B (1991). "Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant ... Griffin JH, Gruber A, Fernández JA (1992). "Reevaluation of total, free, and bound protein S and C4b-binding protein levels in ... different roles for protein S and the protein S-C4b binding protein complex". Blood. 103 (4): 1192-201. doi:10.1182/blood-2003- ...
Outer membrane protein A from E. coli, Ubiquitous surface protein 1 and 2 from Moraxella. Complement C4b-Binding Protein at the ... C4b-binding protein (C4BP) is a protein involved in the complement system where it acts as inhibitor. C4BP has an octopus-like ... C4BP accelerates decay of C3-convertase and is a cofactor for serine protease factor I which cleaves C4b and C3b. C4BP binds ... proline arginine-rich end leucine-rich repeat protein (PRELP), streptococcal M-proteins, gonococcal porins, ...
... complement receptor 1 (CR1), C4b-binding protein and Factor H. Convertase assembly is suppressed by the proteolytic cleavage of ... C4b-binding protein inhibits the haemolytic function of cell-bound C4b. C4b-binding protein and C3b inactivator control the C3 ... Binding β1H to C3b increases C3bINA binding, while factor B binding prevents C3bINA binding and is competitive with β1H binding ... C3b (and C4b) as mediated by Factor I in the presence of membrane cofactor protein (MCP, CD46), C4b-binding protein, CR1, or a ...
2005). "Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/ ... "Complement factor H and related proteins: an expanding family of complement-regulatory proteins?". Immunol. Today. 15 (3): 121- ... 2007). "Binding of human factor H-related protein 1 to serum-resistant Borrelia burgdorferi is mediated by borrelial complement ... Complement factor H-related protein 1 is a protein that in humans is encoded by the CFHR1 gene. GRCh38: Ensembl release 89: ...
C4-binding protein. Membrane cofactor protein is a widely distributed C3b/C4b binding regulatory glycoprotein of the complement ... CR1 can bind to C4b and C3b complexes, whereas CR2 (murine and human) binds to C3dg-bound complexes. CR1, a surface protein ... LHR-A binds preferentially to the complement component C4b: LHR-B and LHR-C bind to C3b and also, albeit with a lower affinity ... Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in ...
C4b-binding protein (C4BP). Decay-accelerating factor (DAF or CD55) Factor H (fH) Other soluble complement regulators that do ... "regulators of complement activation (RCA)" or "complement control proteins (CCP)". Complement control proteins work in concert ... Complement control proteins also play a role in malignancy. Complement proteins protect against malignant cells- both by direct ... Most of the complement control proteins act on the convertases, C3b.Bb and C4b.2a, which are bimolecular complexes formed early ...
Protein S circulates in human plasma in two forms: approximately 60 percent is bound to complement component C4b β-chain while ... decreased protein S activity: decreased free protein S levels (normal total protein S levels) In terms of treatment for protein ... decreased protein S activity: decreased total protein S levels, as well as decreased free protein S levels Type II - decreased ... In regards to the mechanism of protein S deficiency, Protein S is principally made in liver cells. Protein S is a cofactor of ...
C4b-binding protein, factor I, S protein or clusterin, the membrane-bound inhibitors are CR1, membrane cofactor protein (MCF), ... Besides complement particles C1q and C3b which help to opsonize the apoptotic cells, also thrombospondin, pentraxins (C- ... Collectins (e.g. mannose-binding lectin and surfactant protein A) bind the altered surface sugars on apoptotic cell and enable ... As an example, CD14 normally binds lipopolysaccharide (LPS) on the surface of gram-negative bacteria but can also recognize LPS ...
... is a protein belonging to the collectin family that is produced by the liver and can initiate the complement cascade by binding ... C4b tends to bind to bacterial cell membranes. If it is not then inactivated, it will combine with C2b to form the classical C3 ... are bound by MBL. Mannan-binding lectin, also called mannose-binding protein, ... Classical complement pathway Alternative complement pathway Mannan-binding lectin Wallis R, Mitchell DA, Schmid R, Schwaeble WJ ...
... the MASP protein functions to cleave the blood protein C4 into C4a and C4b. The C4b fragments can then bind to the surface of ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... Mannose-binding lectin (MBL), also called mannose-binding protein or mannan-binding protein (MBP), is a lectin that is ... One way that the most-recently discovered lectin pathway is activated is through mannose-binding lectin protein. MBL binds to ...
C5 convertase is also formed by the Classical Pathway when C3b binds C4b and C2a. C5a is an important chemotactic protein, ... In the classical pathway, C4 binds to Ig-associated C1q and C1r2s2 enzyme cleaves C4 to C4b and 4a. C4b binds to C1q, antigen- ... Over 30 proteins and protein fragments make up the complement system, including serum proteins, and cell membrane receptors. ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ...
The classical complement pathway can be initiated by the binding of antigen-antibody complexes to the C1q protein. The globular ... The activated C1s cleaves C4 into C4a and C4b, and C2 into C2a and C2b. The larger and active fragments, C4b and C2b form ... These globular regions of C1q can also bind to bacterial and viral surface proteins, apoptotic cells, and acute phase proteins ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ...
The classical pathway C5 convertase is composed of the larger fragments of complement proteins, C4b, C2b produced by cleavage ... a binding site for a plasma protein called Factor B is also exposed. Factor B then binds to C3b and is cleaved by a plasma ... The binding of C5 is influenced by C6 and C7, components which are thought to act subsequent to it in the complement sequence. ... Target of function The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = ...
The C1 complex (complement component 1, C1) is a protein complex involved in the complement system. It is the first component ... for example by binding to pentraxins such as C-reactive protein or directly to the surface of pathogens. Such binding of C1q ... Active C1s splits C4 and then C2, producing C4a, C4b, C2a and C2b. The classical pathway C3-convertase (C4bC2b complex) is ... Activation of the C1 complex initiates the classical complement pathway. This occurs when C1q binds to antigen-antibody ...
The complement system is a part of the innate immune response. C3b, C4b, and C1q are important complement molecules that serve ... IgM antibodies also bind to PC. Collectin molecules such as mannose-binding lectin (MBL), surfactant protein A (SP-A), and SP-D ... Complement receptor 1 is expressed on all phagocytes and recognizes a number of complement opsonins, including C3b and C4b ... In both cases C1q activates complement, resulting in the cells being marked for phagocytosis by C3b and C4b. C1q is an ...
... formation of the C3-convertase and C5-convertases requires binding of C2 to an activated surface-bound C4b in the presence of ... Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical ... It is thought that cleavage of C2 by C1s, while bound to C4b, results in a conformational rotation of C2b whereas the released ... Kam CM, McRae BJ, Harper JW, Niemann MA, Volanakis JE, Powers JC (Mar 1987). "Human complement proteins D, C2, and B. Active ...
... binding the C4b subunit and releasing C4a into the bloodstream; similarly, binding of C2 causes release of C2b. Together, MBL, ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... these proteins contain a nucleotide binding site (NBS) for nucleoside triphosphates. Interaction with other proteins (e.g. the ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ...
In lieu of the membrane attack complex, complement proteins (particularly C3b and C4b) are deposited on red blood cells. This ... Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response ... In the formation of the membrane attack complex, several complement proteins are inserted into the red blood cell membrane, ... It is a form of autoimmune hemolytic anemia, specifically one in which antibodies only bind red blood cells at low body ...
MASP-2 is activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. Mannan-binding lectin Mannan-binding ... Mannan-binding lectin serine protease 2 also known as mannose-binding protein-associated serine protease 2 (MASP-2) is an ... The encoded proteins are members of the trypsin family of peptidases. MASP-2 is involved in the complement system. MASP-2 is ... The Ra-reactive factor (RARF) is a complement-dependent bactericidal factor that binds to the Ra and R2 polysaccharides ...
CR1 can bind to C4b and C3b complexes, whereas CR2 (murine and human) binds to C3dg-bound complexes. CR1, a surface protein ... is a protein that in humans is encoded by the CR2 gene. CR2 is involved in the complement system. It binds to iC3b (inactive ... Complement receptor 2 has been shown to interact with CD19. Epstein-Barr virus (EBV) binds to B cells at CR2 during infection ... 1987). "A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32". J. ...
... complement factor i MeSH D12.776.124.486.274.920.662 -- complement c4b-binding protein MeSH D12.776.124.486.274.930 -- ... complement c4a MeSH D12.776.124.486.274.350.260 -- complement c4b MeSH D12.776.124.486.274.450 -- complement c5 MeSH D12.776. ... complement c1 inactivator proteins MeSH D12.776.124.486.274.920.250.500 -- complement c1 inhibitor protein MeSH D12.776.124.486 ... mannose-binding protein-associated serine proteases MeSH D12.776.124.486.274.860.450 -- complement factor d MeSH D12.776. ...
... either C3b or C4b) and a cofactor protein (Factor H, CR1, MCP or C4BP). Upon binding of the enzyme to the substrate:cofactor ... Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. Complement ... that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. Factor I deficiency in turn leads to ... Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ (Jun 2010). "Mutations in alternative pathway complement proteins in ...
protein binding. • hydrolase activity. • metal ion binding. • identical protein binding. • serine-type endopeptidase activity. ... Complement component 1s (EC 3.4.21.42, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... complement activation, lectin pathway. • complement activation. • regulation of complement activation. Sources:Amigo / QuickGO ... Busby TF, Ingham KC (May 1990). "NH2-terminal calcium-binding domain of human complement C1s- mediates the interaction of C1r- ...
Complement Factor I Antibody (Internal), Rabbit Anti Human Polyclonal Antibody validated in WB, IHC-P (ALS17749), Abgent ... Responsible for cleaving the alpha-chains of C4b and C3b in the presence of the cofactors C4-binding protein and factor H ... Complement component I, Complement component factor i, Factor I, FI, KAF, I factor, I factor (complement), C3b-INA, Complement ... The Autophagy Receptor Motif Plotter predicts and scores autophagy receptor binding sites in your protein. Identifying proteins ...
C4-binding protein, and factor H), as well as several other complement and non-complement proteins. The remainder of the MCP ... a regulatory molecular of the complement system with cofactor activity for the factor I-mediated inactivation of C3b and C4b, ... The deduced full-length MCP protein consists of a 34-amino acid signal peptide and a 350-amino acid mature protein. The protein ... Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46). ...
Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b. ... Binding of human complement component C4b-binding protein (C4BP) to Streptococcus pyogenes involves the C4b-binding site. J. ... Interaction of C4-binding protein with cell-bound C4b. A quantitative analysis of binding and the role of C4-binding protein in ... Binding of Flavivirus Nonstructural Protein NS1 to C4b Binding Protein Modulates Complement Activation. Panisadee Avirutnan, ...
C4b-binding protein (C4BP), an important inhibitor of complement activation, has a unique spider-like shape. It is composed of ... C4b-binding protein (C4BP), an important inhibitor of complement activation, has a unique spider-like shape. It is composed of ... Structural requirements for the intracellular subunit polymerization of the complement inhibitor C4b-binding protein.. Kask, ... article{5be1f4a6-d9f6-43e4-84be-f1c903a8b6fe, abstract = {C4b-binding protein (C4BP), an important inhibitor of complement ...
The Complement Regulator C4b-Binding Protein (C4BP) Interacts with both the C4c and C4dg Subfragments of the Parent C4b Ligand ...
C4b-binding protein (C4BP) is a potent soluble inhibitor of the classical and lectin pathways of complement. This large (500 ... Functions of human complement inhibitor C4b-binding protein in relation to its structure. ... Both types of subunit are almost exclusively composed of complement control protein (CCP) domains. In recent years, detailed ... Considering the destructive potential of the complement cascade, it is no surprise that there are several complement inhibitors ...
Home » Publications » THE ALFA7BETA0 ISOFORM OF THE COMPLEMENT REGULATOR C4B-BINDING PROTEIN INDUCES A SEMIMATURE, ANTI- ... THE ALFA7BETA0 ISOFORM OF THE COMPLEMENT REGULATOR C4B-BINDING PROTEIN INDUCES A SEMIMATURE, ANTI-INFLAMMATORY STATE IN ... THE ALFA7BETA0 ISOFORM OF THE COMPLEMENT REGULATOR C4B-BINDING PROTEIN INDUCES A SEMIMATURE, ANTI-INFLAMMATORY STATE IN ...
... uses exclusively protein H to bind the complement inhibitor C4b-binding protein (C4BP). We found a strong correlation between ... Binding of Complement Inhibitor C4b-binding Protein to a Highly Virulent Streptococcus pyogenes M1 Strain Is Mediated by ... Binding of Complement Inhibitor C4b-binding Protein to a Highly Virulent Streptococcus pyogenes M1 Strain Is Mediated by ... C4BP bound to immobilized protein H or AP1 bacteria retained its cofactor activity for degradation of (125)I-C4b. Furthermore, ...
... regulated antigen 1 of Candida albicans binds the human complement inhibitor C4b-binding protein and mediates fungal complement ... regulated antigen 1 of Candida albicans binds the human complement inhibitor C4b-binding protein and mediates fungal complement ... Candida albicans binds and utilizes human complement inhibitors, such as C4b-binding protein (C4BP), Factor H, and FHL-1 for ... Candida Pra1 represents the first fungal C4BP-binding surface protein. Pra1, via binding to C4BP, mediates human complement ...
C4b-binding protein (C4BP), a major regulator of the classical pathway of complement activation, also has capacity to regulate ... Lack of association between polymorphisms in C4b-binding protein and atypical Haemolytic Uraemic Syndrome in the Spanish ... Dysregulation of the alternative pathway of complement activation, caused by mutations or polymorphisms in the genes encoding ... factor H, membrane co-factor protein, factor I or factor B, is associated strongly with predisposition to atypical haemolytic ...
Complement, the first line of defence in the host, acts on these bacteria to opsonize with various components of comple ... Complement C4b-Binding Protein. Complement Factor H / metabolism. Complement System Proteins / metabolism*. Endothelial Cells ... 0/C4BPA protein, human; 0/Complement C4b-Binding Protein; 0/Histocompatibility Antigens; 80295-65-4/Complement Factor H; 9007- ... that the inhibitory effect of complement proteins is the result of the bound complement inhibitors C4b-binding protein, in the ...
Binding of the complement inhibitor C4b-binding protein to Lyme disease Borreliae. ... Complement regulator-acquiring surface proteins of Borrelia burgdorferi: a new protein family involved in complement resistance ... Complement-mediated serum sensitivity among spirochetes that cause Lyme disease.. van Dam AP, Oei A, Jaspars R, Fijen C, Wilske ... Complement evasion by Borrelia burgdorferi: serum-resistant strains promote C3b inactivation.. Alitalo A, Meri T, Rämö L, ...
Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b. ... Binding of human complement component C4b-binding protein (C4BP) to Streptococcus pyogenes involves the C4b-binding site. J. ... Many strains of Streptococcus pyogenes bind C4b-binding protein (C4BP), an inhibitor of complement activation. The binding is ... Human C4b-Binding Protein Has Overlapping, But Not Identical, Binding Sites for C4b and Streptococcal M Proteins. Anna M. Blom ...
Binding of Complement Inhibitor C4b-binding Protein to a Highly VirulentStreptococcus pyogenesM1 Strain Is Mediated by Protein ... Yersinia enterocolitica Serum Resistance Proteins YadA and Ail Bind the Complement Regulator C4b-Binding Protein ... Interaction between Complement Regulators and Streptococcus pyogenes: Binding of C4b-Binding Protein and Factor H/Factor H-Like ... Acquisition of Complement Inhibitor Serine Protease Factor I and Its Cofactors C4b-Binding Protein and Factor H by Prevotella ...
Binding of flavivirus nonstructural protein NS1 to C4b binding protein modulates complement activation. ... Antagonism of the complement component C4 by flavivirus nonstructural protein NS1.. Avirutnan P, Fuchs A, Hauhart RE, Somnuke P ... Complement-mediated neutralization of dengue virus requires mannose-binding lectin.. Avirutnan P, Hauhart RE, Marovich MA, ... Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. ...
Complement Systems: Methods and Protocols is composed of 32 individual chapters that describe a variety of protocols to purify ... and analyze the activity of the individual complement components or path ... Purification and Functional Characterization of C4b-Binding Protein (C4BP) Frida C. Mohlin, Anna M. Blom ... Assay for Estimation of the Functional Activity of the Mannan-Binding Lectin Pathway of the Complement System ...
Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was ... Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was ... CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To ... However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the ...
M. Potempa, J. Potempa, M. Okroj et al., "Binding of complement inhibitor C4b-binding protein contributes to serum resistance ... Gingipains can also attach to C4b binding protein avoiding destruction by complement mediated lysis [63]. ... regulatory proteins (Factor H, C4 binding protein), and protection by the bacterial cell wall. In the latter, either the MAC is ... S. K. Singhrao, J. W. Neal, B. P. Morgan, and P. Gasque, "Increased complement biosynthesis by microglia and complement ...
The Pneumococcal Surface Proteins PspA and PspC Sequester Host C4-Binding Protein To Inactivate Complement C4b on the Bacterial ... Human L-ficolin, a recognition molecule of the lectin activation pathway of complement, activates complement by binding to ... Respiratory syncytial virus increases the virulence of Streptococcus pneumoniae by binding to penicillin binding protein 1a. A ... The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. ...
Outer membrane protein A from E. coli, Ubiquitous surface protein 1 and 2 from Moraxella. Complement C4b-Binding Protein at the ... C4b-binding protein (C4BP) is a protein involved in the complement system where it acts as inhibitor. C4BP has an octopus-like ... C4BP accelerates decay of C3-convertase and is a cofactor for serine protease factor I which cleaves C4b and C3b. C4BP binds ... proline arginine-rich end leucine-rich repeat protein (PRELP), streptococcal M-proteins, gonococcal porins, ...
2010) Human complement regulators C4b-binding protein and C1 esterase inhibitor interact with a novel outer surface protein of ... 1998) Lyme disease-causing Borrelia species encode multiple lipoproteins homologous to peptide-binding proteins of ABC-type ... 2004) Analysis of differences in the functional properties of the substrate binding proteins of the Borrelia burgdorferi ... these proteins are the surface lipoproteins vlp and vsp, which are also known to be its main proinflammatory proteins (30). The ...
Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H ...
Outer membrane protein YadA, the Yersinia adhesin, is one of the plasmid-encoded virulence factors of yersiniae. To evaluate ... Yersinia enterocolitica Serum Resistance Proteins YadA and Ail Bind the Complement Regulator C4b-Binding Protein. *Vesa ... Mycobacterial laminin-binding histone-like protein mediates collagen-dependent cytoadherence.. *André Alves Dias, Dominique ... Outer membrane protein YadA, the Yersinia adhesin, is one of the plasmid-encoded virulence factors of yersiniae. To evaluate ...
"Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein". FEBS Letters. 271 (1-2): 131-6. ... Complement C4-A is a protein that in humans is encoded by the C4A gene. This gene encodes the acidic form of complement factor ... "Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity". The ... The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma ...
  • This junction alters the configuration of the protein molecules exposing a hydrophobic site on C7 that allows the C7 to insert into the phospholipid bilayer of the pathogen. (wikipedia.org)
  • The deduced full-length MCP protein consists of a 34-amino acid signal peptide and a 350-amino acid mature protein. (rupress.org)
  • The remainder of the MCP protein consists of 25 amino acids that are rich in serine and threonine (probable site of heavy O-linked glycosylation of MCP), 17 amino acids of unknown significance, and a 23-amino acid transmembrane hydrophobic region followed by a 33-amino acid cytoplasmic tail. (rupress.org)
  • Similar hydrophobic sites on C8 and C9 molecules are exposed when they bind to the complex, so they can also insert into the bilayer. (wikipedia.org)
more