8dgu

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Current revision (09:33, 17 October 2024) (edit) (undo)
 
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dgu OCA], [https://pdbe.org/8dgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dgu RCSB], [https://www.ebi.ac.uk/pdbsum/8dgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dgu ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dgu OCA], [https://pdbe.org/8dgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dgu RCSB], [https://www.ebi.ac.uk/pdbsum/8dgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dgu ProSAT]</span></td></tr>
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</table>
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== Function ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</ref> mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, 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. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]
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== Publication Abstract from PubMed ==
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Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.
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Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease.,Zhou P, Song G, Liu H, Yuan M, He WT, Beutler N, Zhu X, Tse LV, Martinez DR, Schafer A, Anzanello F, Yong P, Peng L, Dueker K, Musharrafieh R, Callaghan S, Capozzola T, Limbo O, Parren M, Garcia E, Rawlings SA, Smith DM, Nemazee D, Jardine JG, Safonova Y, Briney B, Rogers TF, Wilson IA, Baric RS, Gralinski LE, Burton DR, Andrabi R Immunity. 2023 Mar 14;56(3):669-686.e7. doi: 10.1016/j.immuni.2023.02.005. Epub , 2023 Feb 16. PMID:36889306<ref>PMID:36889306</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 8dgu" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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Current revision

Crystal structure of SARS-CoV-2 spike stem helix peptide in complex with Fab of broadly neutralizing antibody CC25.106 isolated from a vaccinated COVID-19 convalescent

PDB ID 8dgu

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