7wqv

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Current revision (09:19, 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=7wqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wqv OCA], [https://pdbe.org/7wqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wqv RCSB], [https://www.ebi.ac.uk/pdbsum/7wqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wqv 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=7wqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wqv OCA], [https://pdbe.org/7wqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wqv RCSB], [https://www.ebi.ac.uk/pdbsum/7wqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wqv ProSAT]</span></td></tr>
</table>
</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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Neutralizing antibodies (nAbs) are important assets to fight COVID-19, but most existing nAbs lose the activities against Omicron subvariants. Here, we report a human monoclonal antibody (Ab08) isolated from a convalescent patient infected with the prototype strain (Wuhan-Hu-1). Ab08 binds to the receptor-binding domain (RBD) with pico-molar affinity (230 pM), effectively neutralizes SARS-CoV-2 and variants of concern (VOCs) including Alpha, Beta, Gamma, Mu, Omicron BA.1 and BA.2, and to a lesser extent for Delta and Omicron BA.4/BA.5 which bear the L452R mutation. Of medical importance, Ab08 shows therapeutic efficacy in SARS-CoV-2-infected hACE2 mice. X-ray crystallography of the Ab08-RBD complex reveals an antibody footprint largely in the beta-strand core and away from the ACE2-binding motif. Negative staining electron-microscopy suggests a neutralizing mechanism through which Ab08 destructs the Spike trimer. Together, our work identifies a nAb with therapeutic potential for COVID-19.
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A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy.,Meng L, Zha J, Zhou B, Cao L, Jiang C, Zhu Y, Li T, Lu L, Zhang J, Yang H, Feng J, Gu Z, Tang H, Jiang L, Li D, Lavillette D, Zhang X PLoS Pathog. 2023 Jan 27;19(1):e1011085. doi: 10.1371/journal.ppat.1011085. , eCollection 2023 Jan. PMID:36706160<ref>PMID:36706160</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 7wqv" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
== References ==
<references/>
<references/>

Current revision

Crystal structure of a neutralizing monoclonal antibody (Ab08) in complex with SARS-CoV-2 receptor-binding domain (RBD)

PDB ID 7wqv

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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