8vpf
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of SARS-CoV spike in complex with CoV1-65 Fab (NTD-bound)== | |
| + | <StructureSection load='8vpf' size='340' side='right'caption='[[8vpf]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8vpf]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus Severe acute respiratory syndrome coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VPF FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=8vpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vpf OCA], [https://pdbe.org/8vpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vpf RCSB], [https://www.ebi.ac.uk/pdbsum/8vpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vpf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SPIKE_SARS SPIKE_SARS] May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.<ref>PMID:31199522</ref> Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:14670965</ref> <ref>PMID:15496474</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]<ref>PMID:19321428</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The function of the spike protein N terminal domain (NTD) in coronavirus (CoV) infections is poorly understood. However, some rare antibodies that target the SARS-CoV-2 NTD potently neutralize the virus. This finding suggests the NTD may contribute, in part, to protective immunity. Pansarbecovirus antibodies are desirable for broad protection, but the NTD region of SARS-CoV and SARS-CoV-2 exhibit a high level of sequence divergence; therefore, cross-reactive NTD-specific antibodies are unexpected, and there is no structure of a SARS-CoV NTD-specific antibody in complex with NTD. Here, we report a monoclonal antibody COV1-65, encoded by the IGHV1-69 gene, that recognizes the NTD of SARS-CoV S protein. A prophylaxis study showed the mAb COV1-65 prevented disease when administered before SARS-CoV challenge of BALB/c mice, an effect that requires intact fragment crystallizable region (Fc) effector functions for optimal protection in vivo. The footprint on the S protein of COV1-65 is near to functional components of the S2 fusion machinery, and the selection of COV1-65 escape mutant viruses identified critical residues Y886H and Q974H, which likely affect the epitope through allosteric effects. Structural features of the mAb COV1-65-SARS-CoV antigen interaction suggest critical antigenic determinants that should be considered in the rational design of sarbecovirus vaccine candidates. | ||
| - | + | , PMID:39589795<ref>PMID:39589795</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8vpf" style="background-color:#fffaf0;"></div> |
| - | [[Category: Bangaru | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Severe acute respiratory syndrome coronavirus]] | ||
| + | [[Category: Bangaru S]] | ||
| + | [[Category: Ward AB]] | ||
Current revision
Structure of SARS-CoV spike in complex with CoV1-65 Fab (NTD-bound)
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