View source for 7ye9


==SARS-CoV-2 Spike (6P) in complex with 3 R1-32 Fabs==
<StructureSection load='7ye9' size='340' side='right'caption='[[7ye9]], [[Resolution|resolution]] 4.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ye9]] 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_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YE9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YE9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7ye9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ye9 OCA], [https://pdbe.org/7ye9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ye9 RCSB], [https://www.ebi.ac.uk/pdbsum/7ye9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ye9 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 ==
Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis of epitope location, neutralization mechanism and analysis of antibody binding to spike variants, we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of the identified population antibody response. These substitutions, including L452R (present in the Delta variant), disrupt interactions mediated by the VH1-69-specific hydrophobic HCDR2 to impair antibody-antigen association, enabling variants to escape. The first Omicron variants were sensitive to antibody R1-32 but subvariants that harbour L452R quickly emerged and spread. Our results provide insights into how SARS-CoV-2 variants emerge and evade host immune responses.

SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope.,He P, Liu B, Gao X, Yan Q, Pei R, Sun J, Chen Q, Hou R, Li Z, Zhang Y, Zhao J, Sun H, Feng B, Wang Q, Yi H, Hu P, Li P, Zhang Y, Chen Z, Niu X, Zhong X, Jin L, Liu X, Qu K, Ciazynska KA, Carter AP, Briggs JAG, Chen J, Liu J, Chen X, He J, Chen L, Xiong X Nat Microbiol. 2022 Oct;7(10):1635-1649. doi: 10.1038/s41564-022-01235-4. Epub , 2022 Sep 23. PMID:36151403<ref>PMID:36151403</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ye9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Chen L]]
[[Category: Chen X]]
[[Category: Gao X]]
[[Category: He J]]
[[Category: Li Z]]
[[Category: Liu B]]
[[Category: Xiong X]]