The importance of ErbB receptors in development is proven from the analysis of genetically modified mice. Indeed, null mutations in individual ErbB loci are lethal. More specifically, depending upon the genetic background of the host, loss of ErbB1 leads to embryonic or perinatal lethality with mice showing abnormalities in multiple organs including the brain, skin, lung and gastrointestinal tract (Miettinen et al., 1995; Sibilia and Wagner, 1995; Threadgill et al., 1995; Sibilia et al., 1998). ErbB2 null mice die at midgestation (E10.5) due to trabeculae malformation in the heart (Lee et al., 1995), a phenotype that is shared by ErbB4 knockout mice (Gassmann et al., 1995). In addition, through genetic rescue of heart development via myocardial expression of an ErbB2 transgene, a further role for ErbB2 in peripheral nervous system development has been demonstrated (Morris et al., 1999). In the case of ErbB3, most knockout mice die by E13.5, displaying normal heart trabeculation but defective ...

The ErbB family of receptors is dysregulated in a number of cancers, and the signaling pathway of this receptor family is a critical target for several anti-cancer drugs. Therefore, a detailed understanding of the mechanisms of receptors activation is critical. However, despite a plethora of biochemical studies and single particle tracking experiments, the early molecular mechanisms involving epidermal growth factor (EGF) binding and EGF receptor (EGFR) dimerization are not as well understood. Due to the large disparity of time and length scales involved in receptor dimerization reactions, we adapt the coarse-grained Monte Carlo (CGMC) simulation framework to enable the simulation of in vivo receptor diffusion and dimerization. Using the CGMC method, spatial modeling of ligand-mediated membrane receptor dimerization reaction dynamics was performed. Furthermore, the simulations demonstrate the importance of spatial heterogeneity in membrane receptor localization. Mathematical models, especially ...

Background In todays research, we describe heterodimerization between human-Somatostatin Receptor 5 (hSSTR5) and 2-Adrenergic Receptor (2AR) and its own effect on the receptor trafficking, coupling to adenylyl cyclase and signaling including mitogen activated protein kinases and calcineurin-NFAT pathways. receptor heterodimerization. Bottom line These data for the very first time unveil a book understanding for the function of hSSTR5/2AR in the modulation of signaling pathways which includes not been dealt with earlier. strong course=kwd-title Keywords: G-protein-coupled receptor, Individual somatostatin receptor-5; 2 adrenergic receptors; Heterodimerization; Photobleaching-fluorescence resonance energy transfer and Somatostatin History We have lately defined homo-and heterodimerization of somatostatin receptor (SSTR) subtypes and its own functional implications on receptor trafficking and signaling in response to agonist activation. SSTRs heterodimerization isnt restricted to its family ...

Abstract: Ni functionalized metal organic frameworks (MOF) are promising heterogeneous ethene dimerization catalysts. Activities comparable to or higher than Ni-aluminosilicates have been reported in literature. However, unlike the Ni-aluminosilicates, those Ni-MOFs require a large excess of co-catalyst to initiate the dimerization process and some catalysts generate polymers which lead to catalyst deactivation. Herein, we report a series of Ni(II) and 2,2′-bipyridine-5,5′-dicarboxylate (bpy) functionalized UiO-67 MOF that catalyze the ethene dimerization reaction co-catalyst free. The catalysts were active for ethene dimerization (up to 850 mg butene gcat-1 h-1) after activation at 300 °C in 10 % O2 for 360 min and subsequent exposure to flowing ethene (P(ethene) =26 bar, 250 °C) for 240 min. The catalysts yielded up to 6 % conversion with 99 % selectivity to linear 1- and 2-butenes, which formed in non-equilibrated ratios. Overall, the test data indicate that all three linear butenes are ...

Full title: Berry phase induced dimerization in one-dimensional quadrupolar systems. Lecturer: Karlo Penc (Wigner Res. Inst.). We investigate the effect of the Berry phase on quadrupoles that occur, for example, in the low-energy description of spin models. Specifically, we study here the one-dimensional bilinear-biquadratic spin-one model. An open question for many years about this model is whether it has a nondimerized fluctuating nematic phase. The dimerization has recently been proposed to be related to Berry phases of the quantum fluctuations. We use an effective low-energy description to calculate the scaling of the dimerization according to this theory and then verify the predictions using large scale density-matrix renormalization group simulations, giving good evidence that the state is dimerized all the way up to its transition into the ferromagnetic phase. We furthermore discuss the multiplet structure found in the entanglement spectrum of the ground state wave functions.. ...

To test the hypothesis that the difference in the directions of DNA bending induced by transcription activation domains linked to the bZIP region of Fos versus Jun was due to a preferred orientation of heterodimer binding to the AP‐1 site, we examined bending at additional binding sites. The relative directions of DNA bending induced by the transcription activation domains fused to the Fos versus Jun bZIP domains at the M, X, MX, XM and X6G sites were similar (Figure 5), suggesting that Fos-Jun heterodimers bind to these sites in the same preferred orientation. These AP‐1 sites share an asymmetric central C:G base pair. To examine the influence of this central base pair on the orientation of heterodimer binding and to explore the relationship between binding orientation and DNA bending, we examined DNA bending at two sites that contained a central G:C base pair. One site (W) is identical to the M site with the exception of transversion of the central C:G base pair to a G:C base pair. The ...

To understand how SAS-6 might organise the centriolar cartwheel, we obtained high-resolution crystal structures of SAS-6 fragments at beamlines ID29 and BM14. These structures show that SAS-6 consists of a globular N-terminal head domain and a rod like coiled-coil domain that follows in sequence. Both domains were found to form homodimers: The N-terminal domain formed a slightly curved head-to-head dimer while the coiled-coil domain formed a canonical elongated coiled-coil dimer. We confirmed these interactions in solution and showed that the coiled-coil dimer is stable while head-to-head dimerisation occurs with a rather low affinity. Both interactions are biologically relevant and are essential for SAS-6 function in vivo.. Modelling these interactions in SAS-6 resulted in curved oligomers that were compatible with a 9-fold ring with similar dimensions to that of cartwheel hubs observed in vivo (Figure 117b). Consistent with this model, we found that recombinant SAS-6 constructs do indeed form ...

A RECOMBINANT ECTODOMAIN OF THE RECEPTOR FOR THE STEM-CELL FACTOR (SCF) RETAINS LIGAND-INDUCED RECEPTOR DIMERIZATION AND ANTAGONIZES SCF-STIMULATED CELLULAR-RESPONSES

There are ten isozymes of adenylyl cyclases in mammals, adenylyl cyclase type I-X, (ADCY I-X); In mammals adenylyl cyclase plays an important role in signal transduction pathways in which cAMP is a secondary messenger[13]. ADCY I-IX all share a general structure; They are composed of two trans-membrane regions (M1, M2) which are composed of six membrane-spanning helices and function to keep the enzyme anchored in the membrane, and two cytoplasmic regions (C1, C2) which can be further sub divided (C1a, C1b, C2a, C2b) and are responsible for all catalytic activity, and regulation by G-proteins and forskolin[13]. In solution, the C1a and C2a domains can form heterodimers with each other, either in the same or different enzymes, or they can form homodimers with their identical units on different enzymes[3]. The C1b domain is very large (≈15 kDa) with many regulatory sites, and has a variable structure across isozymes; while the C2b domain is nearly non-existent in many isozymes, and has yet to be ...

There are ten isozymes of adenylyl cyclases in mammals, adenylyl cyclase type I-X, (ADCY I-X); In mammals adenylyl cyclase plays an important role in signal transduction pathways in which cAMP is a secondary messenger[12]. ADCY I-IX all share a general structure; They are composed of two trans-membrane regions (M1, M2) which are composed of six membrane-spanning helices and function to keep the enzyme anchored in the membrane, and two cytoplasmic regions (C1, C2) which can be further sub divided (C1a, C1b, C2a, C2b) and are responsible for all catalytic activity, and regulation by G-proteins and forskolin[12]. In solution, the C1a and C2a domains can form heterodimers with each other, either in the same or different enzymes, or they can form homodimers with their identical units on different enzymes[3]. The C1b domain is very large (≈15 kDa) with many regulatory sites, and has a variable structure across isozymes; while the C2b domain is nearly non-existent in many isozymes, and has yet to be ...

The discovery of potent and selective prostamide antagonists provided definitive evidence for a separate pharmacological entity and, in turn, impetus for cloning the receptor. Clues for the identity of the receptor were provided by taking into account the existent, pertinent information at that point in time. This is summarized as follows: 1) prostamide F2α and bimatoprost-responsive preparations also responded to PGF2α (although in many cases PGF2α activation was not accompanied by responses to prostamide F2α and its analogs); 2) bimatoprost-induced ocular hypotensive activity was abolished in FP receptor knockout mice (Crowston et al., 2005; Ota et al., 2005); 3) an FP receptor mRNA splicing variant was shown to be active (Pierce et al., 1997, Fujino et al., 2000); 4) prostanoid receptor heterodimerization was shown to create novel activation/binding sites (Wilson et al., 2004). These data suggested that the FP receptor gene was key to encoding the prostamide receptor. Thus, attention was ...

Thus, caspase-8 has a crucial pro-survival role in shutting off RIPK1 and preventing it from inducing necroptosis. But how, then, does a cell wherein caspase-8 is activated not die by apoptosis instead? How does it live to develop into a healthy mouse or human? Caspase-8 activates through dimerization; two molecules of caspase-8 are forcefully brought together to form an active complex. The previously mentioned adapter protein FADD is essential for initiating this process of dimerization, but recent evidence has shown that once a few dimers are formed around clusters of FADD, more caspase-8 dimers can form independent of FADD. An important clue comes from the observation that caspase-8 does not only activate when it dimerises with itself to form a homodimer, but can also when it forms a dimer with its cousin, FLIP (FLICE-like Inhibitory Protein), to form a heterodimer. FLIP is similar to caspase-8 but has no protease activity, it is an inactive caspase homologue. The heterodimer is active, but ...

TY - JOUR. T1 - Establishment of a new detection system for the dimerization of IRE1α by BiFC assay. AU - Shinjo, Satoko. AU - Tashiro, Etsu. AU - Imoto, Masaya. N1 - Funding Information: We would like to thank Dr. Atsushi Miyawaki for kindly providing cDNA of cerulean. This work is supported by Grants-in-Aid for Scientific Research (KAKENHI grant no. 23510283, to E.T.) from Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. S.S. was a research assistant for the Global COE Program for Human Metabolomic Systems Biology.. PY - 2013. Y1 - 2013. N2 - We developed a new detection system for the activation of an endoplasmic reticulum (ER) stress sensor, inositol requiring kinase 1 α (IRE1α), by evaluating dimerization of it by bimolecular fluorescence complementation (BiFC) assay. By detecting the fluorescence derived from the reconstituted cerulean, this assay system enabled us to distinguish the activation behaviors of IRE1α as to ER stress-inducing compounds.. AB - We ...

HNF1 homeobox A (hepatocyte nuclear factor 1 homeobox A), also known as HNF1A, is a human gene on chromosome 12. It is ubiquitously expressed in many tissues and cell types. The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes. Mutations in the HNF1A gene have been known to cause diabetes. The HNF1A gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. The HNF1A gene resides on chromosome 12 at the band 12q24.2 and contains 9 exons. This gene produces 8 isoforms through alternative splicing. This protein belongs to the HNF1 homeobox family. It contains 3 functional domains: an N-terminal dimerization domain (residues 1-32), a bipartite DNA-binding motif containing an atypical POU-homeodomain (residues 98-280), and a C-terminal transactivation domain (residues 281-631). There is also a flexible linker (residues 33-97) which connects ...

Shop Jun dimerization protein ELISA Kit, Recombinant Protein and Jun dimerization protein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.

1K68: Crystal structures of two cyanobacterial response regulators in apo- and phosphorylated form reveal a novel dimerization motif of phytochrome-associated response regulators

Procaspase-3 is the dimeric precursor of the apoptosis-executioner caspase-3 that displays little activity in vitro. The interface of the procaspase-3 dimer plays a critical role in zymogen maturation, although the active sites are not located at the dimer interface. We show that replacement of valine 266, the residue at the center of the procaspase-3 dimer interface, with arginine or glutamate results in an increase in enzyme activity of about 25-60-fold, representing a pseudo-activation of the procaspase. In contrast, substitution of V266 with histidine abolishes the activity of the procaspase-3 as well as that of the mature caspase. This mutant can be activated by protein exposure at pH 5, followed by dialysis at neutral pH. While the mutations do not affect the dimeric properties of the procaspase, we show that the V266E mutation may affect the formation of a loop bundle that is important for stabilizing the active sites. In contrast, the V266H mutation affects the positioning of loop L3, ...

The major findings of this study are as follows: (1) Adeno-virus-mediated gene transfer of c-jun and c-fos can effectively and specifically establish an experimental model for AP-1 activation in human ECs, (2) AP-1 activation can directly induce gene expression of an adhesion molecule, ICAM-1, and a chemokine, MCP-1, which are considered to be the molecular markers of EC activation and are implicated in various EC pathological processes, from inflammation to atherogenesis, (3) The AP-1-mediated induction of ICAM-1 can occur independently of activation of the NF-κB pathway.. AP-1 transcription factors are formed through dimerization between the members of the Fos and Jun families.27 Recent studies have suggested AP-1 to be an important regulator in endothelial function and pathological processes. First, the AP-1 binding motif has been identified as a recurrent sequence in the promoters of many genes biologically significant in the conversion of ECs into a proinflammatory or procoagulant status, ...

GXXXG-Mediated Parallel and Antiparallel Dimerization of Transmembrane Helices and Its Inhibition by Cholesterol: Single-Pair FRET and 2D IR ...

The invention provides a catalytic method for the dimerization or codimerization or oligomerization, particularly selectively, of olefins, carried out under pressure, in a reaction zone 1 containing a solid catalyst bed into which is disposed a plurality of hollow internal spaces 6.3 defined by walls and through which an autogenous thermoregulation fluid flows, in the form of a sheet, after passing through a central distributing zone 6.1 and distributing zones 6.2 and before passing through collecting zones 6.4 and into a central collecting zone 6.5.

The self heating process of Tetrafluoroethylene caused by an exothermic dimerization reaction was studied. The heat of reaction can lead to a thermal explosion by the decomposition of the Tetrafluoroethylene.. Different reaction kinetics, including multistep kinetics, were used to describe the mass balance. The COMSOL Chemical Engineering Module was used to perform the simulation which was validated by experiments and yielded well-correlating results.. ...

Journal Article: Incomplete Peierls-like chain dimerization as a mechanism for intrinsic conductivity and optical transparency: A La-Cu-O-S phase with mixed-anion layers as a case study ...

MORAN, JAMES PAUL, POLAR EFFECTS ON THE RATES OF FORMATION AND DIMERIZATION OF FREE RADICALSFROM ETHYL ACETATE (1963). Doctoral Dissertations. AAI6403549 ...

Thermochemistry of HO2 + HO2 → H2O4: Does HO2 Dimerization Affect Laboratory Studies?: Self-reaction is an important sink for the hydroperoxy radical (HO2) in t

In dimerization To 1-Butene, Axens proposes a portfolio of technology licenses, catalysts, adsorbents and services such as consulting, software or operations support to respond to your operational n

Dimerization ranitidine - All Drugs Without a Prescription. We accept Bitcoin. We work 20 years. We have over 800.000 satisfied customers.

Fingerprint Dive into the research topics of Stoichiometric and Catalytic Dimerization of Conjugated Dienes with (C,sub,5,/sub,R,sub,5,/sub,)Ru(diene),sup,+,/sup,. Together they form a unique fingerprint. ...

Biological Process: cranial nerve development; endocardial cushion development; ERBB2 signaling pathway; heart development; MAPK cascade; negative regulation of cell adhesion; negative regulation of ERBB signaling pathway; negative regulation of neuron apoptosis; negative regulation of secretion; negative regulation of signal transduction; neuron apoptosis; peptidyl-tyrosine phosphorylation; peripheral nervous system development; phosphatidylinositol phosphorylation; phosphoinositide 3-kinase cascade; positive regulation of cardiac muscle tissue development; positive regulation of gene expression; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of protein kinase B signaling; regulation of cell motility; regulation of cell proliferation; Schwann cell differentiation; signal transduction; transmembrane receptor protein tyrosine kinase signaling pathway; wound healing ...

Filament formation is required for most of the functions of actin. However, the intermonomer interactions that stabilize F-actin have not been elucidated because of a lack of an F-actin crystal structure. The Holmes muscle actin model suggests that a

For the past ten years, we have been interested in the human transcription factor PATZ1. This protein is not only important for T lymphocyte development but also has tumor suppressor functions and we have identified that it functionally interacts with the tumor suppressor p53. PATZ1 belongs to the BTB-zinc finger family which has 49 members in mammals. These proteins often suppress transcription by recruiting corepressors and histone deacetylases. Recently we solved the crystal structures of the murine and zebrafish PATZ1 BTB domains (PDB ID: 6GUV and 6GUW) and showed that these proteins form homodimers like most of the other crystallized family members. The mechanism of preferential homodimerization over heterodimerization of these family members is an outstanding question. We are testing several hypotheses: a) preferential degradation of heterodimers (a degron hypothesis), b) structural restrictions of dimer interfaces, c) co-translational dimerization. To assess these models, we have set up a ...

These links are probably not what we want and we should consider revising how the linking script handles them in the future. 1) Paper ID(s): 131227 Linked Term: synaptic membrane Problem: The link links to a WormBase GO term search page 2) Paper ID(s): 128421 Linked Term: transactivation Problem: The link links to a WormBase GO term search page 3) Paper ID(s): 128421 Linked Term: core promoter binding Problem: The link links to a WormBase GO term search page 4) Paper ID(s): 128421, 128389 Linked Term: dimerization Problem: This term should link to the general protein dimerization activity, but instead links to the more specific protein homodimerization activity 5) Paper ID(s): 128389 Linked Term: E-box binding Problem: The link links to a WormBase GO term search page 6) Paper ID(s): 129064, 129486, 110338 Linked Term: embryogenesis Problem: This term is linked to the GO term embryonic development ending in seed dormancy which is too specific and irrelevant to C. elegans. Should ...

On the cover: Twenty-five TLR4 TIR dimer models in which the BB loop of one TIR domain interacts with the E helix of the other. Toshchakov et al. screened a library of TLR4 TIR-derived decoy peptides to demonstrate that peptides derived from these regions inhibit TLR4 signaling by binding to the TLR4 TIR. Toshchakov, V. Y., H. Szmacinski, L. A. Couture, J. R. Lakowicz, and S. N. Vogel. 2011. Targeting TLR4 signaling by TLR4 Toll/IL-1 receptor domain-derived decoy peptides: Identification of the TLR4 Toll/IL-1 receptor domain dimerization interface. J. Immunol. 186: 4819-4827. ...

To understand the mechanisms by which growth factor signaling can modulate the activity of the AR, we have examined the physical and functional interactions between the AR, the scaffold protein RACK1, and the signaling kinase Src. Our findings provide evidence that RACK1 mediates androgen and growth factor cross-talk by facilitating the interaction of the AR with the Src tyrosine kinase.. RACK1, which was initially identified as a binding protein for PKC ( 5), was subsequently shown to interact with a wide range of signaling molecules and thus can serve as a platform for integrating diverse signaling activities. Src and the AR are among the reported binding partners for RACK1 ( 7, 13). In our study, we showed that the RACK1-AR interaction occurs in LNCaP cells at endogenous levels of protein expression and that the interaction is enhanced when cells are treated with androgen. Interestingly, we found that, when RACK1 and the AR are overexpressed by transient transfection, the dimeric interaction ...

CRI is driven mainly by cells of the innate immune system, predominantly TAMs (2, 34). Previous reports point to the importance of V-ATPases in tumor progression and migration (6, 8, 35). Other investigators have described the fundamental role of V-ATPase during cytokine trafficking and secretion (36-38). Our studies bridge the gap between these two research areas by showing that a peptide signal of V-ATPase origin participates in the induction of an inflammatory response from monocytes.. We show that incubation of monocytes with a2NTD leads to upregulation of several genes/proteins involved in M2 polarization. a2NTD induces an M2-like phenotype in monocytes (Fig. 2) described as IL-12low, IL-23low, and IL-10high (16). The increased levels of IL-10 correspond to the significant levels of p50 in the nucleus after a2NTD stimulation (Fig. 3D). Whereas p50 homodimers are traditionally associated with transcriptional repression (39), p50 induces IL-10 transcription by binding the IL-10 promoter in ...

As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.

MMLs stimulate WhNV 480-44-4 protein A self-interaction by selling the homotypic and heterotypic interactions of protein A. (A) MBP-tagged protein A fragments

|P>PKA (Protein Kinase-A) is an enzyme that regulates processes as diverse as growth, development, memory, and metabolism. In its inactivated state, PKA exists as a tetrameric complex of two Catalytic subunits (PKA-C) and a Regulatory (PKA-R) subunit dimer. To date, [...]

Induce specific interactions between two different proteins. Previously available from ARIAD as the ARGENT Regulated Heterodimerization Kit & AP21967.

Induce specific interactions between two different proteins. Previously available from ARIAD as the ARGENT Regulated Heterodimerization Kit & AP21967.

TY - JOUR. T1 - Zinc finger protein 131 inhibits estrogen signaling by suppressing estrogen receptor α homo-dimerization. AU - Oh, Yohan. AU - Chung, Kwang Chul. PY - 2013/1/4. Y1 - 2013/1/4. N2 - Steroid hormone estrogen elicits various physiological functions, many of which are mediated through two structurally and functionally distinct estrogen receptors, ERα and ERβ. The functional role of zinc finger protein 131 (ZNF131) is poorly understood, but it is assumed to possess transcriptional regulation activity due to the presence of a DNA binding motif. A few recent reports, including ours, revealed that ZNF131 acts as a negative regulator of ERα and that SUMO modification potentiates the negative effect of ZNF131 on estrogen signaling. However, its molecular mechanism for ERα inhibition has not been elucidated in detail. Here, we demonstrate that ZNF131 directly interacts with ERα, which consequently inhibits ERα-mediated trans-activation by suppressing its homo-dimerization. Moreover, ...

The dimerization of the cationic β-hairpin antimicrobial peptide protegrin-1 (PG1) is investigated in three different environments: water, the surface of a lipid bilayer membrane, and the core of the membrane. PG1 is known to kill bacteria by forming oligomeric membrane pores, which permeabilize the cells. PG1 dimers are found in two distinct, parallel and antiparallel, conformations, known as important intermediate structural units of the active pore oligomers. What is not clear is the sequence of events from PG1 monomers in solution to pores inside membranes. The step we focus on in this work is the dimerization of PG1. In particular, we are interested in determining where PG1 dimerization is most favorable. We use extensive molecular dynamics simulations to determine the potential of mean force as a function of distance between two PG1 monomers in the aqueous subphase, the surface of model lipid bilayers and the interior of these bilayers. We investigate the two known distinct modes of dimerization

BmrA from Bacillus subtilis is a half-size ABC (ATP-binding cassette) transporter involved in multidrug resistance. Although its supramolecular organization has been investigated after reconstitution in a lipid bilayer environment, and shows a dimeric and possibly a tetrameric form, the precise quaternary structure in a detergent-solubilized state has never been addressed. In the present study, BmrA was purified from Escherichia coli membranes using an optimized purification protocol and different detergents. Furthermore, the ATPase activity of BmrA and the quantity of bound lipids and detergent were determined, and the oligomeric state was analysed using SEC (size-exclusion chromatography) and analytical ultracentrifugation. The activity and the quaternary structure of BmrA appeared to be strongly influenced by the type and concentration of the detergent used. SEC data showed that BmrA could be purified in a functional form in 0.05 and 0.01% DDM (n-dodecyl-β-D-maltoside) and was homogeneous ...

The precursor protein of von Willebrand factor (pro-vWF) consists of four different repeated domains, denoted D1-D2-D-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2, followed by a carboxy-terminal region of 151 amino acids without obvious internal homology. Previously, we have shown the requirement of the domains D1, D2, D, and D3 of pro-vWF in the assembly of pro-vWF dimers into multimers. Here, we define the domains of vWF involved in dimerization, using deletion mutants of full-length vWF cDNA transiently expressed in monkey kidney COS-1 cells. It is shown that only the carboxy-terminal 151 amino acid residues of vWF are required for dimerization. In addition, by analyzing a construct, encoding only the carboxy-terminal 151 amino acids of vWF, we find that the formation of dimers is an event independent of other domains present on pro-vWF, such as the domains C1 and C2 previously suggested to be involved in dimerization. Furthermore, it is shown that a deletion mutant of vWF, lacking the carboxy-terminal ...

The epidermal growth factor receptor (EGFR) is activated by dimerization, but activation also generates higher-order multimers, whose nature and function are poorly understood. We have characterized ligand-induced dimerization and multimerization of EGFR using single-molecule analysis, and show that multimerization can be blocked by mutations in a specific region of Domain IV of the extracellular module. These mutations reduce autophosphorylation of the C-terminal tail of EGFR and attenuate phosphorylation of phosphatidyl inositol 3-kinase, which is recruited by EGFR. The catalytic activity of EGFR is switched on through allosteric activation of one kinase domain by another, and we show that if this is restricted to dimers, then sites in the tail that are proximal to the kinase domain are phosphorylated in only one subunit. We propose a structural model for EGFR multimerization through self-association of ligand-bound dimers, in which the majority of kinase domains are activated cooperatively, ...

Complex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Homeobox TFs in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, demonstrating remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. Here, we sought to delineate whether TALE-TALE heterodimerization is ancestral to eukaryotes. We analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the

Background: The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and stability of the microtubule system. In this paper the role of dimerization in its microtubulerelated functions is established, and an approach is proposed to evaluate thermodynamic constants for multiple equilibrium systems from ITC measurements. Methods: For structural studies size exclusion chromatography, SDS-PAGE, chemical cross-linking, circular dichroism, fluorescence spectroscopy and isothermal titration calorimetry were used; the functional effect was analyzed by tubulin polymerization assay. Numerical simulation of the multiple equilibrium was performed with Mathematica software. Results: The dimerization of TPPP/p25 is promoted by elevation of the protein concentration and by GTP addition. The dimeric form displaying enhanced tubulin polymerization promoting activity is stabilized by disulfide bond or chemical cross-linking. The GTP binding to the dimeric form ...

Previous studies have indicated that the G protein-coupled secretin receptor is present as a homo-dimer, organized through symmetrical contacts in transmembrane domain IV, and that receptor dimerization is critical for high potency signalling by secretin. However, whether all of the receptor exists in the dimeric form or if this is regulated, is unclear. We used measures of quantal brightness of the secretin receptor tagged with monomeric enhanced green fluorescent protein (mEGFP) and Spatial Intensity Distribution Analysis to assess this. Calibration using cells expressing plasma membrane-anchored forms of mEGFP initially allowed demonstration that the Epidermal Growth Factor receptor is predominantly monomeric in the absence of ligand and whilst wild type receptor was rapidly converted to a dimeric form by ligand, a mutated form of this receptor remained monomeric. Equivalent studies showed that at moderate expression levels the secretin receptor exists as a mixture of monomeric and dimeric ...

Negative Binding Cooperativity within CCR2/CCR5 Heterodimers. We next tested further the pharmacological properties of CCR5/CCR2 heterodimers using binding assays. We demonstrated previously that CCR2/CCR5 heterodimers can only bind a single chemokine with high affinity (El Asmar et al., 2005). These observations suggested either an overlap between the two chemokine binding sites of the monomers or some kind of negative allosteric interaction across the dimer interface (Springael et al., 2005). It was also shown for another class I receptor (TSHr) that a single ligand molecule binds to a receptor dimer (Urizar et al., 2005), and a similar observation has been made recently for a receptor belonging to class 3 (Kniazeff et al., 2004; Urizar et al., 2005). To determine more precisely the mechanism underlying these effects, we built on the model of chemokine receptor dimers and performed dissociation kinetics experiments after extensive ligand dilution, a procedure that constitutes the classic way ...

Book 4-benzylamino benzo-anellated pyrrolo[2,3-the N-1 from the pyrimidine partial framework (Amount 1) as proven for erlotinib in Amount 213. utilised without additional purification. The bromo-substituted benzylamines have already been synthesized 7.33 (ddd, 7.18 (dd, 7.32C7.27 (7.36 (d, 3.69 (4.62 (d, 4.62 (d, 4.47 (d, 3.69 (4.61 (d, 4.60 (d, 2.24 (3.69 (s, 3H, CH3), 4.60 (d, 3.69 (2.24 (3.70 (were determined using the 154039-60-8 formula: IC50?=?1/2 [beliefs of our focus on substances 5aCh, 6aCc and 7 for the tyrosine receptor kinases IGF-1R and EGFR. beliefs [M]receptor heterodimerization resulted in a proceeding of the aggressive tumor development as defined24. Therefore there have been intense attempts to develop novel inhibitors of EGFR and IGF-1R. We investigated the inhibitory activity towards both kinases EGFR and IGF-1R for our novel benzo-anellated pyrrolo[2,3-value of 0.101?M and to a submicromolar affinity towards IGF-1R with 0.537?M. So compound 5d is definitely a first dual ...

The dimerization interface in VraR is essential for induction of the cell wall stress response in Staphylococcus aureus: a potential druggable target. https://t.co/9mtzsf5GDw. ...

Activation helix orientation of estrogen receptor is mediated by receptor dimerization: evidence from molecular dynamics simulations

Glutamyl tRNA-reductase dimerization domain family domain assignments . Domain assignment details for each protein include region, Evalue and model. Alignments, domain architectures and domain combinations are provided for each group of proteins.

TY - JOUR. T1 - Oligomerization properties of GCN4 leucine zipper e and g position mutants. AU - Zeng, Xiangang. AU - Zhu, Hai. AU - Lashuel, Hilal A.. AU - Hu, James C.. PY - 1997/10/1. Y1 - 1997/10/1. N2 - Putative intersubunit electrostatic interactions between charged amine acids on the surfaces of the dimer interfaces of leucine zippers (g-e ion pairs) have been implicated as determinants of dimerization specificity. To evaluate the importance of these ionic interactions in determining the specificity of dimer formation, we constructed a pool of ,65,000 GCN4 leucine zipper mutants in which all the e and g positions are occupied by different combinations of alanine, glutamic acid, lysine, or threonine. The oligomerization properties of these mutants were evaluated based on the phenotypes of cells expressing λ repressor-leucine zipper fusion proteins. About 90% of the mutants do not form stable homooligomers. Surprisingly, approximately 8% of the mutant sequences have phenotypes consistent ...

In this study, using in silico screening targeting the critical dimerization core residues following detailed analysis of the buried surface area, we successfully identified a hit compound (LQZ-7) and a potential lead inhibitor (LQZ-7F) that can bind directly to survivin and cause proteasome-dependent survivin degradation. LQZ-7F has an IC50 of 0.4 to 4.4 μmol/L against multiple cell lines of different human cancers and induces spontaneous apoptosis. It is also effective in suppressing xenograft tumor growth and reduces survivin level in xenograft tumors.. This study provides a proof of concept that the dimerization core units in the dimeric interface of undruggable homodimeric proteins can be targeted for drug discovery. Combining computational analysis of the dimeric interface to first identify these core units with in silico screening, as demonstrated here, is likely a viable approach that will help succeed in identifying small-molecule compounds inhibiting dimerization of the target ...

Fingerprint Dive into the research topics of Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation. Together they form a unique fingerprint. ...

Several conclusions can be drawn:. (i) The sequence of PHF6 at the beginning of the third repeat (exon 11) is present in all τ isoforms and provides an explanation why all τ isoforms can form PHFs. The counterpart PHF6* lies at the beginning of R2 (exon 10) and is therefore present only in τ isoforms containing four repeats. If the two hotspots for β-sheet formation operated in a cooperative fashion, they could possibly enhance PHF assembly, and this might explain why PHF formation is enhanced in dementias where the four-repeat isoforms are overrepresented (e.g., FTDP-17; see refs. 31-33).. (ii) Dimerization of τ via oxidation of Cys-322 into an intermolecular disulfide bridge strongly promotes PHF assembly (5). The results shown here argue that the peptide containing Cys-322 (peptide 318-335; Fig. 5) does not promote PHF assembly by itself. However, dimerization at Cys-322 could bring two PHF6 motifs into close vicinity, which would facilitate β-sheet interactions. In this view, ...

Progression through the cell cycle is essential for the continued existence of all uni- and multicellular organisms. It is crucial for the survival of a cell that its DNA is correctly replicated. In mammals, the onset of DNA replication is regulated by the activity of the heterodimeric E2F-DP transcription factor. The mammalian E2F family contains six proteins (E2F1, E2F2, E2F3, E2F4, E2F5 and E2F6) (Trimarchi and Lees, 2002). All E2Fs have an N-terminally located DNA-binding domain immediately followed by a dimerization domain, allowing them to pair with a dimerization partner (DP1 or DP2). Dimerization of E2F with DP is a prerequisite for high affinity, sequence-specific binding to the E2F consensus DNA-binding site. E2F activity is negatively regulated by retinoblastoma (Rb), which binds to the transcriptional activation domain of the E2F-DP factor, rendering it inactive. Moreover, the recruitment by Rb of DNA-modifying enzymes, such as histone deacetylases and polycomb proteins, leads to ...

The Bcl-2 oncoprotein is a potent inhibitor of apoptosis and is overexpressed in a variety of different malignancies. Bcl-2 function is regulated through heterodimerization with other members of the Bcl-2 protein family. In addition, several proteins that are not members of the Bcl-2 family can bind to Bcl-2, including BAG-1 protein. In this study, we screened for proteins that bind to Bcl-2, and isolated two additional members of the BAG-1 protein family, BAG-3 and BAG-4. The BAG-4 protein that we cloned also corresponds to the recently isolated suppressor of death domains (SODD) protein, a molecule that binds and inhibits signaling by tumor necrosis factor receptor 1 (TNFR1). Both BAG-3 and BAG-4/SODD were found to physically associate with Bcl-2, and both proteins are well conserved from human to mouse. A region of homology, comprising 68 amino acids, is present in the carboxyl termini of BAG-3 and BAG-4/SODD, and this region corresponds with sequences termed BAG domains that are found in ...

Hughes, C. E. and Pollitt, A. Y. and Mori, J. and Eble, J. A. and Tomlinson, Michael G. and Hartwig, J. H. and OCallaghan, C. A. and Futterer, K. and Watson, Steve P (2010) CLEC-2 activates Syk through dimerization. Blood, 115 (14). p. 2947. ISSN 0006-4971. Severin, S. and Pollitt, A. Y. and Navarro-Nunez, L. and Nash, C. A. and Mourao-Sa, D. and Eble, J. A. and Senis, Y. A. and Watson, Steve P (2011) Syk-dependent Phosphorylation of CLEC-2: A Novel Mechanism of Hem-Immunoreceptor Tyrosine-Based Activation Motif Signaling. Journal of Biological Chemistry, 286 (6). p. 4107. ISSN 0021-9258. ...

Retrovirus capsid dimerization domain-like alignments. Alignments can be refined by adding alignments from other genomes, adding your own sequences and/or aligning to other models from the same superfamily. The display of alignments can also be customised.

In recent years, the nuclear receptors (NR) dynamics have been studied extensively by various approaches. However, the transition path of helix 12 (H12) to an agonist or an antagonist conformation and the exchange pathway between these states is not clear yet. A number of accelerated molecular dynamics (aMD)

α-Cleavage and generation of the GPI-anchored C-terminal PrPC1 fragment and the secreted N-terminal PrPN1 fragment is a typical posttranslational modification of PrPC. The importance of the α-cleavage is illustrated by increasing evidence that both PrPN1 and PrPC1 represent potential therapeutic molecules for the treatment of prion diseases (Westergard et al., 2011; Guillot-Sestier et al., 2012). In this study, we show that PrPC homodimerization increases its trafficking to the plasma membrane, and we identify homodimerization as an important mechanism in the control of PrPC1 and PrPN1 levels.. Although we used an artificial strategy to enforce the dimerization of PrPC, we believe that our results are highly relevant to in vivo conditions. A growing number of studies have highlighted the importance of dimerization in the biology of the prion protein. PrPC forms dimers in bovine and mouse brain homogenates, and in neuroblastoma cells (Priola et al., 1995; Meyer et al., 2000; Rambold et al., ...

The invention relates to proteins or polypeptides that comprise intramolecular dimers of fluorescent protein monomers. More specifically, the invention relates to recombinant polypeptides comprising a monomer of a fluorescent polypeptide, a linker peptide, and a second monomer of that fluorescent polypeptide, where the monomers form an intramolecular dimer. The invention also relates to nucleic acids encoding Intramolecular Dimer Fluorescent Proteins (IDFPs) and vectors comprising such nucleic acids. The invention further relates to methods of making IDFPs and methods of using them. IDFPs are, useful in any application suited for fluorescent proteins and are particularly useful in applications in which more than one fluorescent protein sharing complementary dimerization interfaces is present in the same mixture or is expressed in the same cell, because IDFPs do not form heterodimers.

We report the discovery of HD5-CD, an unprecedented C2-symmetric β-barrel-like covalent dimer of the cysteine-rich host-defense peptide human defensin 5 (HD5). Dimerization results from intermonomer disulfide exchange between the canonical α-defensin Cys(II)-Cys(IV) (Cys(5)-Cys(20)) bonds located at …

The evolutionarily well-conserved SecA is essential for bacterial post-translational translocation. SecA uses the energy of ATP to drive preproteins through the membrane pore. The functional oligomeric state of SecA and the molecular basis for recognition of unfolded polypeptides by SecA are major unresolved questions that must be addressed to understand preprotein targeting and the molecular mechanics of SecA-mediated translocation. This thesis will address three aspects of these questions. First, the role of unstructured termini in the oligomerization and function of various SecA constructs was elucidated. By re-examining the tetramerization of a truncated SecA construct (SecA-N68), it was shown that the unstructured polypeptides at its termini are mediating its oligomerization. In turn, by removal of the first 14 N-terminal residues of the functional SecA-N95 construct, dimerization was drastically weakened. Although the weakened dimerization did not significantly affect the solution ATPase activity

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The dimeric nature of triosephosphate isomerases (TIMs) is maintained by a thorough surface area interface of more than 1600 ?2. to dissociate the dimer. Herein we found that the character of residue I45 controls the dimer-monomer equilibrium in TvTIMs. Unfolding experiments employing monomeric and dimeric mutants led us to conclude that dimeric TvTIMs unfold following a four state model denaturation process whereas monomeric TvTIMs follow a three state model. In contrast to other monomeric TIMs monomeric variants of TvTIM1 are stable and unexpectedly one of them (I45A) is only 29-fold less active than wild-type TvTIM1. The high enzymatic activity of monomeric TvTIMs contrast with the marginal catalytic activity of diverse monomeric TIMs variants. The stability of the monomeric variants of TvTIM1 and the use of cross-linking and analytical ultracentrifugation experiments permit us to understand the differences between the catalytic activities of TvTIMs and other marginally active monomeric TIMs. ...

In article ,david-0809991507400001 at mac355.nmus.pwf.cam.ac.uk,, david at cryst.bioc.cam.ac.uk (David) wrote: , Im sorry for not making it clear, but the kind of homogeneity I was , thinking about was with respect to proteins rather than nucleic acids, and , I guess in particular, whether a protein that appears pure on, e.g. a gel , or gel filtration columnm, has higher-order oligomers or aggregates , present. As suggested, good ways to study this include gel filtration and , analytical ultracentrifugation, which we have done for our system, but I , had recently heard the advice that one should always as a first step, look , at the UV280 scan to see if there are aggreagates, which was what prompted , my original question. Remember that absorption of light in mainly due to only 3 aas( trp(~280nm),tyr(~275nm,phe~258nm)). If you have a solution of a monomeric protien in solution or a multimeric protein in solution, the absorption spectra will not reveal it. It will just tell you the ...

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Tetramerization of iGluR subunits is the necessary step to yield functional iGluR complexes that can be inserted into the plasma membrane. Our experiments demonstrate that in AMPARs, the eukaryotic-specific M4 segment is required for tetramerization in both homomeric and heteromeric receptors. AMPAR subunits lacking M4, GluA2(R)-ΔM4, or GluA1-ΔM4 do not tetramerize (Figs. 1C,E, 3) and, consistent with their immature oligomeric status, are retained in the ER (Figs. 1B,D). Additionally, GluA1 or GluA2(R) subunits containing mutations that disrupt helix-helix interactions along a specific face of the M4 α-helix (Fig. 2A), a face that aligns with M1 and M3 of an adjacent subunit (Sobolevsky et al., 2009), also do not form tetramers as assayed by BN-PAGE (Fig. 2C,D) and/or by FSEC (Fig. 2E,F). Finally, manipulations that disrupted tetramerization did not prevent dimerization, suggesting that the initial step of oligomerization is largely intact. Thus, the M4 segment-and its presumed interaction ...

We report the fourth observation of Hb Sallanches [alpha104(G11)Cys--,Tyr, TGC--,TAC (alpha2)], an unstable alpha chain variant of intermediate severity in the homozygous state. Heterozygosity occasionally produces mild hypochromia and microcytosis in some patients. A balanced beta/alpha ratio, found in previously reported cases, points to unstable alphabeta dimers formed as a ...

The technique of analytical ultracentrifugation (AUC) was developed by Svedberg and Lysholm in 1927 (1). With AUC one is able to determine molecular weight, shape and stoichiometry of macromolecules and macromolecular complexes.

Hiragami-Hamada, K.; Sörös, S.; Nikolov, M.; Wilkins, B.; Kreuz, S.; Chen, C.; De La Rosa-Velazquez, I. A.; Zenn, H. M.; Kost, N.; Pohl, W. et al.; Chernev, A.; Schwarzer, D.; Jenuwein, T.; Lorincz, M.; Zimmermann, B.; Walla, P. J.; Neumann, H.; Baubec, T.; Urlaub, H.; Fischle, W.: Dynamic and flexible H3K9me3 bridging via HP1beta dimerization establishes a plastic state of condensed chromatin. Nature Communications 7, 11310 (2016 ...