View source for 7vmu


==Crystal Structure of SARS-CoV Spike Receptor-Binding Domain Complexed with Neutralizing Antibody==
<StructureSection load='7vmu' size='340' side='right'caption='[[7vmu]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7vmu]] is a 2 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_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VMU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VMU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89&#8491;</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=7vmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vmu OCA], [https://pdbe.org/7vmu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vmu RCSB], [https://www.ebi.ac.uk/pdbsum/7vmu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vmu ProSAT]</span></td></tr>
</table>
== Function ==
[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 ==
BACKGROUND: Neutralizing antibodies are approved drugs to treat coronavirus disease-2019 (COVID-19) patients, yet mutations in severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants may reduce the antibody neutralizing activity. New monoclonal antibodies (mAbs) and antibody remolding strategies are recalled in the battle with COVID-19 epidemic. RESULTS: We identified multiple mAbs from antibody phage display library made from COVID-19 patients and further characterized the R3P1-E4 clone, which effectively suppressed SARS-CoV-2 infection and rescued the lethal phenotype in mice infected with SARS-CoV-2. Crystal structural analysis not only explained why R3P1-E4 had selectively reduced binding and neutralizing activity to SARS-CoV-2 variants carrying K417 mutations, but also allowed us to engineer mutant antibodies with improved neutralizing activity against these variants. Thus, we screened out R3P1-E4 mAb which inhibits SARS-CoV-2 and related mutations in vitro and in vivo. Antibody engineering improved neutralizing activity of R3P1-E4 against K417 mutations. CONCLUSION: Our studies have outlined a strategy to identify and engineer neutralizing antibodies against SARS-CoV-2 variants.

Antibody engineering improves neutralization activity against K417 spike mutant SARS-CoV-2 variants.,Li L, Gao M, Jiao P, Zu S, Deng YQ, Wan D, Cao Y, Duan J, Aliyari SR, Li J, Shi Y, Rao Z, Qin CF, Guo Y, Cheng G, Yang H Cell Biosci. 2022 May 17;12(1):63. doi: 10.1186/s13578-022-00794-7. PMID:35581593<ref>PMID:35581593</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7vmu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Cheng G]]
[[Category: Guo Y]]
[[Category: Jiao P]]
[[Category: Rao Z]]
[[Category: Wang W]]
[[Category: Yang H]]