View source for 7tcq


==Crystal structure of SARS-CoV-2 neutralizing antibody WS6 in complex with spike S2 peptide==
<StructureSection load='7tcq' size='340' side='right'caption='[[7tcq]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tcq]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=7TCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TCQ 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]] 2.02&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7tcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tcq OCA], [https://pdbe.org/7tcq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tcq RCSB], [https://www.ebi.ac.uk/pdbsum/7tcq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tcq 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 ==
Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike elicits diverse antibodies, but it is unclear if any of the antibodies can neutralize broadly against other beta-coronaviruses. Here, we report antibody WS6 from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, Middle East respiratory syndrome (MERS)-CoV, and hCoV-OC43. The crystal structure at 2 A resolution of WS6 revealed recognition to center on a conserved S2 helix, which was occluded in both pre- and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion and post-viral attachment. Comparison of WS6 with other recently identified antibodies that broadly neutralize beta-coronaviruses indicated a stem-helical supersite-centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156-to be a promising target for vaccine design.

Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability.,Shi W, Wang L, Zhou T, Sastry M, Yang ES, Zhang Y, Chen M, Chen X, Choe M, Creanga A, Leung K, Olia AS, Pegu A, Rawi R, Schon A, Shen CH, Stancofski ED, Talana CA, Teng IT, Wang S, Corbett KS, Tsybovsky Y, Mascola JR, Kwong PD Structure. 2022 Sep 1;30(9):1233-1244.e7. doi: 10.1016/j.str.2022.06.004. Epub, 2022 Jul 15. PMID:35841885<ref>PMID:35841885</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 7tcq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Kwong PD]]
[[Category: Zhou T]]