View source for 7tla


==Down-state locked rS2d SARS-CoV-2 spike ectodomain in the RBD-down conformation, State 1==
<StructureSection load='7tla' size='340' side='right'caption='[[7tla]], [[Resolution|resolution]] 3.13&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tla]] is a 3 chain structure with sequence from [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=7TLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TLA FirstGlance]. <br>
</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=7tla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tla OCA], [https://pdbe.org/7tla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tla RCSB], [https://www.ebi.ac.uk/pdbsum/7tla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tla 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 ==
Aided by extensive spike protein mutation, the SARS-CoV-2 Omicron variant overtook the previously dominant Delta variant. Spike conformation plays an essential role in SARS-CoV-2 evolution via changes in receptor-binding domain (RBD) and neutralizing antibody epitope presentation, affecting virus transmissibility and immune evasion. Here, we determine cryo-EM structures of the Omicron and Delta spikes to understand the conformational impacts of mutations in each. The Omicron spike structure revealed an unusually tightly packed RBD organization with long range impacts that were not observed in the Delta spike. Binding and crystallography revealed increased flexibility at the functionally critical fusion peptide site in the Omicron spike. These results reveal a highly evolved Omicron spike architecture with possible impacts on its high levels of immune evasion and transmissibility.

Structural diversity of the SARS-CoV-2 Omicron spike.,Gobeil SM, Henderson R, Stalls V, Janowska K, Huang X, May A, Speakman M, Beaudoin E, Manne K, Li D, Parks R, Barr M, Deyton M, Martin M, Mansouri K, Edwards RJ, Eaton A, Montefiori DC, Sempowski GD, Saunders KO, Wiehe K, Williams W, Korber B, Haynes BF, Acharya P Mol Cell. 2022 Jun 2;82(11):2050-2068.e6. doi: 10.1016/j.molcel.2022.03.028. Epub, 2022 Mar 25. PMID:35447081<ref>PMID:35447081</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Acharya P]]
[[Category: Henderson R]]