View source for 7wpf


==SARS-CoV-2 Omicron Variant S Trimer complexed with three JMB2002 Fab==
<StructureSection load='7wpf' size='340' side='right'caption='[[7wpf]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wpf]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama], [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=7WPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WPF 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]] 2.92&#8491;</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=7wpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wpf OCA], [https://pdbe.org/7wpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wpf RCSB], [https://www.ebi.ac.uk/pdbsum/7wpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wpf 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]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.

Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody.,Yin W, Xu Y, Xu P, Cao X, Wu C, Gu C, He X, Wang X, Huang S, Yuan Q, Wu K, Hu W, Huang Z, Liu J, Wang Z, Jia F, Xia K, Liu P, Wang X, Song B, Zheng J, Jiang H, Cheng X, Jiang Y, Deng SJ, Xu HE Science. 2022 Mar 4;375(6584):1048-1053. doi: 10.1126/science.abn8863. Epub 2022 , Feb 8. PMID:35133176<ref>PMID:35133176</ref>

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

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Cao X]]
[[Category: Cheng X]]
[[Category: Deng SJ]]
[[Category: Gu C]]
[[Category: He X]]
[[Category: Hu W]]
[[Category: Huang S]]
[[Category: Huang Z]]
[[Category: Jia F]]
[[Category: Jiang H]]
[[Category: Jiang Y]]
[[Category: Liu J]]
[[Category: Liu P]]
[[Category: Song B]]
[[Category: Wang X]]
[[Category: Wang Z]]
[[Category: Wu C]]
[[Category: Wu K]]
[[Category: Xia K]]
[[Category: Xu HE]]
[[Category: Xu P]]
[[Category: Xu Y]]
[[Category: Yin W]]
[[Category: Yuan Q]]
[[Category: Zheng J]]