• Two populations of liposomes were prepared, both simulating the plasma membrane of target cells, but with the pH of the internal aqueous medium buffered either at pH 7.4 (physiological cytosol pH) or at pH 5.0 (endosomal pH at which influenza virus displays maximal fusion activity). (biomedcentral.com)
  • Taken together, these findings provide strong evidence that the generation of PtdIns(4)P is sufficient to trigger forward transport from the Golgi to the plasma membrane and that Sac1p is critically required for the termination of this signal. (embl.de)
  • Insulin release involves the packaging of insulin in small (diameter approximate to0.3 mum) secretory granules, the trafficking of these granules to the plasma membrane, the exocytotic fusion of the granules with the plasma membrane and eventually the retrieval of the secreted membranes. (lu.se)
  • Evidence from a variety of secretory tissues, including pancreatic islet cells suggests, however, that the secretory granules can be functionally divided into distinct pools that are distinguished by their release competence and/or proximity to the plasma membrane. (lu.se)
  • One of the last steps in the fusion process is overseen by a set of proteins called SNAREs. (nature.com)
  • Exosomal markers include microRNAs like miR-21 and miR-141, plus various proteins that belong in functional groups such as tetraspanins (CD9, CD63 and CD81), heat shock proteins (Hsp70, Hsp73 and Hsp90) and membrane transporters (GTPases) ( 4 ). (spandidos-publications.com)
  • Scientists from the Institut Pasteur and the CNRS, working with the University of Göttingen, have characterized the mechanism used by the virus to insert one of its envelope proteins into the host cell membrane, thereby enabling it to infect the cell. (pasteur.fr)
  • Scientists in the Structural Virology Unit (Institut Pasteur/CNRS) directed by Félix Rey, in collaboration with the University of Göttingen, characterized the mechanism used by the virus to insert one of its surface proteins into the host cell membrane and drive fusion. (pasteur.fr)
  • These string-shaped tether proteins can recognize the Rab5 protein present in a vesicle membrane and bind to it. (innovations-report.com)
  • However, the Atg8 family of proteins are not found solely attached to double-membrane autophagosomes. (babraham.ac.uk)
  • We have shown that this process is triggered by recruitment of ATG16L1 by the vacuolar-type H-translocating ATPase (V-ATPase) proton pump, suggesting a role for pH sensing in recruitment of Atg8-family proteins to single membranes. (babraham.ac.uk)
  • That notion is probably fundamental to all viral fusion proteins-or for that matter to most cellular membrane fusion events facilitated by proteins. (harvard.edu)
  • The recruitment of specific cytosolic proteins to intracellular membranes through binding phosphorylated derivatives of phosphatidylinositol (PtdIns) controls such processes as endocytosis, regulated exocytosis, cytoskeletal organization, and cell signaling. (embl.de)
  • The long term goal of our research is to elucidate the molecular mechanisms by which proteins are targeted to specific and distinct compartments. (stanford.edu)
  • Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. (jove.com)
  • Coat proteins can help sort the cargo and assemble on the donor membrane to initiate vesicle formation. (jove.com)
  • The introduction of fluorescent proteins that can be targeted to the secretory granules, in combination with the advent of new techniques that allow real-time imaging of granule trafficking in living cells (granule dynamics), has led to an explosion of our knowledge of the pre-exocytotic and post-exocytotic processes in the beta cell. (lu.se)
  • While many studies have been focused on the membrane structure, the dynamics of such systems are crucial for the function of the membrane including membrane bound proteins. (lu.se)
  • Native membrane derived polymer-supported lipid bilayers (nSLBs) are poised to bridge the gap between live cell experiments and traditional model membrane architectures that by offering a combination of accessibility by surface sensitive analytical instrumentation and a composition which more closely resembles cellular membranes by displaying a diversity of endogenous membrane proteins, lipids, and carbohydrates. (lu.se)
  • Due to the lack of detergent solubilization and reconstitution steps, the nSLBs created using this approach contain essentially all of the native lipids, as well as the membrane-associated proteins and carbohydrates from the donor membrane. (lu.se)
  • Membrane proteins play a key role in the cell's energy metabolism and in its signalling and communication with its environment. (lu.se)
  • More than half of all drugs that are in use today target membrane proteins. (lu.se)
  • The main aim of the course is to enable students to acquire specialised knowledge and understanding of membrane biochemistry and the molecular structure, topology and functional mechanisms of membrane proteins. (lu.se)
  • The lectures address the three different main types of membrane proteins and associated cellular processes: transport and transporters, signal transduction and receptors, bioenergetics and photosynthetic and respiratory proteins. (lu.se)
  • Lectures dealing with methods for theoretical modelling of membrane protein structure, fusion protein techniques, X-ray crystallography, heterologous expression, solubilisation and purification of membrane proteins are also included in the course. (lu.se)
  • In silico exercise addressing potential problems concerning the detection of heterologously expressed membrane proteins, solubilisation and evaluation of detergent properties, ion exchange chromatography and gel filtering in the presence of a detergent, and control of the protein's stability and integrity after purification. (lu.se)
  • Group discussions about e.g. the similarities/dissimilarities, cloning and overexpression strategies, and structure and function of membrane proteins. (lu.se)
  • The project entails practice in literature searching, project planning and documentation, and provides specialised practical knowledge of expression and management of membrane proteins. (lu.se)
  • Transport occurs in membrane-bounded containers called vesicles, and several protein families have evolved to mediate the budding of a vesicle from the donor compartment, and its transport to and fusion with the target organelle. (nature.com)
  • env codes for the protein that sticks out of the lipid membrane. (scienceblogs.com)
  • To keep using HIV-1 as an example, this precursor protein gets chopped in two, into a t rans m embrane gp41, which stays anchored in the viral membrane, and a s ub u nit gp120, which is noncovalently attached to gp41 like a lolly-pop. (scienceblogs.com)
  • The spike (S) protein found on the surface of the causative agent, the SARS-CoV-2 virus, has been the prime target for current vaccine research since antibodies directed against the S protein were found to neutralize the virus. (mdpi.com)
  • 60% of human protein-coding genes, mostly by binding to the 3′- untranslated region (3′UTR) of the target mRNAs ( 5 ) and, therefore, miRNAs affect gene expression networks of a variety of biological processes including development, apoptosis, proliferation, and metabolism ( 1 , 2 ). (frontiersin.org)
  • Exosomes are one of the most researched classes of extracellular vesicles because they are carriers of targeted protein and DNA/RNA loads. (spandidos-publications.com)
  • They have demonstrated that the viral envelope protein has a "pocket" that specifically recognizes a category of lipids in the cell membrane. (pasteur.fr)
  • They also determined the atomic structure of this new protein-lipid complex, demonstrating that this protein has a "pocket" which specifically recognizes the hydrophilic heads of some of the lipids that make up the cell membrane. (pasteur.fr)
  • It has been hypothesized that conserved histidines in the class II fusion protein E of these viruses function as molecular switches and, by their protonation, control the fusion process. (rupress.org)
  • The Influenza Virus Hemagglutinin: A Model Protein in the Study of Membrane Fusion. (biomedcentral.com)
  • Role of the M2 Protein in Influenza Virus Membrane Fusion: Effects of Amantadine and Monensin on Fusion Kinetics. (biomedcentral.com)
  • Role of Virion M2 Protein in Influenza Virus Uncoating: Specific Reduction in the Rate of Membrane Fusion Between Virus and Liposomes by Amantadine. (biomedcentral.com)
  • These changes are transmitted to the transmembrane protein gp41 and are thought to activate its fusogenic potential by unmasking its fusion peptide (By similarity). (antikoerper-online.de)
  • Surface protein gp120 (SU) may target the virus to gut- associated lymphoid tissue (GALT) by binding host ITGA4/ITGB7 (alpha-4/beta-7 integrins), a complex that mediates T-cell migration to the GALT. (antikoerper-online.de)
  • The transmembrane protein gp41 (TM) acts as a class I viral fusion protein. (antikoerper-online.de)
  • Under the current model, the protein has at hairpin intermediate state, and post-fusion hairpin state. (antikoerper-online.de)
  • The CoV S protein is an envelope glycoprotein that plays a very important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. (nih.gov)
  • It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. (nih.gov)
  • Recent work published in The EMBO Journal and EMBO Reports reveals a novel role for the protein TECPR1 as a sensor for stressed membranes and regulator of lysosomal membrane repair. (babraham.ac.uk)
  • In non-canonical Atg8-family protein lipidation they become conjugated to single membranes. (babraham.ac.uk)
  • Research at Harvard Medical School is shedding new light on the battle line where viral and cell membranes meet, and the key role of a protein grappling hook with which the influenza virus commandeers its prize-your cells. (harvard.edu)
  • To fuse the two membranes, the virus carries a protein called hemagglutinin (the "H" in H1N1). (harvard.edu)
  • Triggered by the acidic environment of an endosome, that protein will extend from the viral membrane and attach, like a grappling hook, to the endosome's membrane. (harvard.edu)
  • Instead, they observed, the protein remains stretched between the two membranes, like a bridge. (harvard.edu)
  • The study also appears to settle a question about the nature of the hemagglutinin protein, and viral fusion: Are multiple hooks needed because they interact directly with each other to fuse the membranes, or because that's the number required to pull the somewhat elastic membranes together by brute force? (harvard.edu)
  • Protein modules such as FVYE domains and PH domains that bind specifically to PtdIns 3-phosphate (PtdIns-3-P) and polyphosphoinositides, respectively, can direct such membrane targeting. (embl.de)
  • Mounting evidence suggests that the genetic disorders/mutation and diseases change not only the protein expression patterns but also membranes themselves. (lu.se)
  • This is followed by experimental determination using genetic construction and expression of a fusion protein of the membrane protein and a marker protein in a bacterial system which is subsequently analysed. (lu.se)
  • An individually planned and executed minor project during two weeks, in which the students express a membrane protein of their choice and demonstrate in some way that the expression was successful. (lu.se)
  • A two-component molecular motor placing vesicles proximal to endosomal membranes. (innovations-report.com)
  • Analysis of this HA gene shows that it is closely related to avian A(H5) viruses in HA clade 2.3.4.4b and lacked amino acid changes that improve recognition of mammalian receptors or fusion of the viral membrane with the host endosomal membranes. (cdc.gov)
  • A(H5) viruses in HA clade 2.3.4.4b and lacked amino acid changes that improve recognition of mammalian receptors or fusion of the viral membrane with the host endosomal membranes. (cdc.gov)
  • During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. (antikoerper-online.de)
  • In my talk, I will show you some examples how such biological cues influence the dynamic properties of membranes. (lu.se)
  • gp41, the transmembrane subunit, mediates fusion of viral and cellular membranes [ 3 ]. (plos.org)
  • The entry of enveloped viruses into host cells involves a fusion step between the viral and a cellular membrane. (rupress.org)
  • After binding of the S1 subunit RBD on the virion to its receptor on the target cell, the HR1 and HR2 domains interact with each other to form a six-helix bundle (6-HB) fusion core, bringing viral and cellular membranes into close proximity for fusion and infection. (nih.gov)
  • The region modeled in this cd (SD-1 and SD-2, the S1/S2 cleavage region, and the S2 fusion subunit) plays an essential role in viral entry by initiating fusion of the viral and cellular membranes. (nih.gov)
  • Non-canonical autophagy is a key cellular pathway in immunity, cancer, and neurodegeneration, characterized by conjugation of ATG8 to endolysosomal single membranes (CASM). (babraham.ac.uk)
  • These have been suggested to be the core machinery that mediates the fusing of two membranes, as well as ensuring that vesicles deliver their cargo to the right compartment 1 , 2 . (nature.com)
  • We are studying the mechanism of viral membrane fusion and its inhibition by drugs and antibodies. (stanford.edu)
  • Some of our studies are aimed at creating an HIV vaccine that elicits antibodies against a transient, but vulnerable, intermediate in the membrane-fusion process, called the pre-hairpin intermediate. (stanford.edu)
  • Neutralizing antibodies (NAbs) can block virus entry by binding Env and inhibiting attachment or conformational changes required for fusion [ 4 - 7 ]. (plos.org)
  • The HA is also the primary target of neutralizing antibodies elicited by infection or vaccination, and the HA of virus from this specimen is very closely related (99% identity) to the A/Astrakhan/3212/2020-like pre-pandemic candidate vaccine viruses (e.g. (cdc.gov)
  • Theyre coated in the membranes of the cells they budded off of. (scienceblogs.com)
  • It is responsible for binding to new host cells and mediating fusion between the viral membrane, and the target cell membrane. (scienceblogs.com)
  • Recently, miRNA exocytosis by vesicle fusion in response to stimulation was observed in chromaffin cells, which are neuroendocrine cells in the sympathetic nervous system ( 24 ). (frontiersin.org)
  • Their multi‑functional cargo have been indicated to regulate a vast number of biological pathways in target cells. (spandidos-publications.com)
  • RVF virus spreads in its host by fusing with cell membranes so that it can proliferate and infect other cells. (pasteur.fr)
  • Understanding the mechanism used by these viruses for insertion in the cell membrane paves the way for the development of therapeutic agents that target the "pocket" involved in the fusion of viral and cell membranes with the aim of preventing pathogenic arboviruses from entering host cells. (pasteur.fr)
  • Entry of Semliki Forest Virus into Cells: Effects of Concanamycin A and Nigericin on Viral Membrane Fusion and Infection. (biomedcentral.com)
  • The hemagglutinin (HA) gene codes for one of the two surface glycoproteins and is central to species specificity because it is responsible for virus attachment and fusion with host cells. (cdc.gov)
  • We show that CGS21680 raises lysosomal calcium levels and rescues mitochondrial functionality (mitochondrial inner membrane potential and expression of the complex IV of the mitochondrial respiratory chain), which is compromised in NPC1 cells. (jneurosci.org)
  • Moreover, we identify a distinct, N-terminal, higher affinity interaction interface between LRRK2 phosphorylated Rab8 and Rab10 termed 'Site #2', that can retain LRRK2 on membranes in cells to catalyze multiple, subsequent phosphorylation events. (stanford.edu)
  • In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. (antikoerper-online.de)
  • In addition to the lysosomal compartment, mitochondria have been described as relevant targets of the NPC1 pathogenesis. (jneurosci.org)
  • Because studies from our laboratory have demonstrated that chitinase 3-like-1 (CHI3L1) stimulates ACE2 and Spike (S) priming proteases that mediate SC2 infection, studies were undertaken to determine if interventions that target CHI3L1 are effective inhibitors of SC2 viral variant infection. (elifesciences.org)
  • COPII vesicles are formed in the ER membranes and mediate transport from ER to the Golgi. (jove.com)
  • These bend the membrane to form a bud that is released from the donor membrane as a vesicle. (jove.com)
  • They observed that three or four hemagluttinin hooks must attach in close proximity to fuse the membranes. (harvard.edu)
  • An influenza virus is a collection of eight RNA strands enclosed in a lipid-bilayer membrane. (harvard.edu)
  • We recently developed a generic method for producing polymer-supported lipid bilayers directly from cell-derived native membrane vesicles (NMVs). (lu.se)
  • Microvesicles have a diameter ranging from 100 nm to 1 µm and are released by cell membrane budding. (spandidos-publications.com)
  • They are derived by a targeted mechanism from the cell endocytic compartment and are formed and stored within the intracellular multivesicular bodies (MVBs). (spandidos-publications.com)
  • Virus-Cell and Cell-Cell Fusion. (biomedcentral.com)
  • The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. (antikoerper-online.de)
  • Complete fusion occurs in host cell endosomes. (antikoerper-online.de)
  • When the virus encounters a cell-in your lung, for example-that cell may engulf the virus inside an internal membrane called an endosome. (harvard.edu)
  • A particle according to any one of the preceding claims, wherein heterologous polypeptide sterically hinders fusion of an enveloped viral particle with an eukaryotic cell to which it is bound. (sumobrain.com)
  • Coated vesicles are transport vesicles that bud off from specialized regions of the cell membrane. (jove.com)
  • As cell membranes are both dynamic and compositionally complex, replicating these aspects in a model membrane are essential. (lu.se)
  • By monitoring fusion using the R18 assay, we found that the internal pH of the target liposomes did not influence membrane merging as mediated by the influenza virus hemagglutinin, thus demonstrating that a transmembrane pH gradient is not required in this fusion process. (biomedcentral.com)
  • The S2 subunit comprises the fusion peptide (FP), a second proteolytic site (S2'), followed by an internal fusion peptide (IFP) and two heptad-repeat domains (HR1 and HR2) preceding the transmembrane domain (TM). (nih.gov)
  • We focus on the Rab GTPases that are master regulators of membrane trafficking. (stanford.edu)
  • The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. (antikoerper-online.de)
  • A Common Mechanism for Influenza Virus Fusion Activity and Inactivation. (biomedcentral.com)
  • Understanding these interactions should pave the way for the identification of new therapeutic strategies that target viruses transmitted by these mosquitoes. (pasteur.fr)
  • the identification of new therapeutic targets remains a priority. (jneurosci.org)
  • Munc18-1 is a part of this fusion machinery, but its role is controversial because it is indispensable for fusion but also inhibits the assembly of purified SNAREs in vitro . (jneurosci.org)
  • The controversy would be solved if binding to closed syntaxin1 were shown to be stimulatory for vesicle fusion and/or additional essential interactions were identified between Munc18-1 and the fusion machinery. (jneurosci.org)
  • The flavivirus membrane fusion machinery, like that of many other enveloped viruses, is triggered by the acidic pH in endosomes after virus uptake by receptor-mediated endocytosis. (rupress.org)
  • The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains the coronavirus fusion machinery and is primarily alpha-helical. (nih.gov)
  • While the noncanonical autophagy pathway shares the common ATG machinery, it bears key mechanistic and functional distinctions, and is characterized by conjugation of ATG8 to single membranes (CASM). (babraham.ac.uk)
  • By repeatedly contracting and expanding, this molecular motor functions similarly to a classical Stirling engine and helps to distribute cargo to membrane-bound organelles. (innovations-report.com)
  • Substances can be transported from one membrane-encased compartment to another, but the compartments maintain their unique identities. (nature.com)
  • None of the Munc18 variants affected vesicle fusion kinetics or fusion pore duration. (jneurosci.org)
  • In a third model, Munc18-1 actively promotes SNARE complex formation and vesicle fusion. (jneurosci.org)
  • Researchers from Dresden and Bangalore discover a unique two-component molecular motor that uses a kind of renewable chemical energy to pull vesicles toward membrane-bound organelles. (innovations-report.com)
  • And that's an intriguing target, said Stephen Harrison , the study's senior author and the Giovanni Armenise-Harvard Professor of Basic Biomedical Science in the department of Biological Chemistry and Molecular Pharmacology at HMS. (harvard.edu)
  • A molecular understanding of membrane traffic has broad implications for our understanding of growth control in cancer, receptor trafficking errors in heart disease, regulation of insulin secretion in diabetes and synaptic vesicle biogenesis and transport in neurological disorders. (stanford.edu)
  • Thus, CHI3L1 is a universal, VOC-independent therapeutic target in COVID-19. (elifesciences.org)
  • This group contains the SD-1 and SD-2 subdomains of the S1 subunit C-terminal domain (C-domain), the S1/S2 cleavage region, and the S2 fusion subunit of the spike (S) glycoprotein from betacoronaviruses in the nobecovirus subgenus (D lineage), including Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9). (nih.gov)
  • Indeed, sphingosine storage leads to a decrease in Ca 2+ levels in the acidic compartment and, consequently, fusion/trafficking processes are compromised. (jneurosci.org)
  • the cytoplasmic tail (CT) of gp41 (endodomain) is considered to be entirely contained inside the virion [ 9 , 10 ] and consequently is thought not to be targeted by the host immune response. (plos.org)
  • A feed-forward pathway drives LRRK2 kinase membrane recruitment and activation. (stanford.edu)
  • Using the mutational analysis of recombinant subviral particles of tick-borne encephalitis virus, we provide direct experimental evidence that the initiation of fusion is crucially dependent on the protonation of one of the conserved histidines (His323) at the interface between domains I and III of E, leading to the dissolution of domain interactions and to the exposure of the fusion peptide. (rupress.org)
  • To address the possibility that activation of phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR/FRAP), represents one of these pathways, we have examined the effect of simultaneous inhibition of the Ras-MAPK and PI3K-mTOR pathways on transformation of CEF by v-Src. (embl.de)
  • To escape that bubble, the virus fuses its membrane with the endosome's, opening a window into the cell's interior. (harvard.edu)
  • In order to catalyze the membrane fusion reaction, CoV S needs to be primed through cleavage at the S1/S2 and S2' sites. (nih.gov)
  • Similar defects in membrane trafficking are caused by the overexpression of PIK1. (embl.de)
  • These conformational changes are activated by specific triggers, allowing fusion to occur at the right time and at the right place in the viral life cycle. (rupress.org)
  • Influenza Hemagglutinin-Mediated Membrane Fusion: Influence of Receptor Binding on the Lag Phase Preceding Fusion. (biomedcentral.com)
  • HN - 2008 BX - Lateral Sinus MH - Atrial Septum UI - D054087 MN - A07.541.459.249 MS - The thin membrane-like muscular structure separating the right and the left upper chambers (HEART ATRIA) of a heart. (bvsalud.org)
  • That observation helps us distinguish between classes of models for a stage of the fusion process," Harrison said. (harvard.edu)
  • Membrane Fusion Activity of Influenza Virus. (biomedcentral.com)
  • Target Membrane Sialic Acid Modulates both Binding and Fusion Activity of Influenza Virus Biochim . (biomedcentral.com)
  • The flu virus carries about 300 to 400 of these hooks, and virologists had known that several are needed to fuse the membranes. (harvard.edu)