View source for 9nxy


==Cryo-EM structure of SARS-CoV-2 spike S2' trimer==
<StructureSection load='9nxy' size='340' side='right'caption='[[9nxy]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9nxy]] 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=9NXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NXY 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]] 3.08&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <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=9nxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9nxy OCA], [https://pdbe.org/9nxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9nxy RCSB], [https://www.ebi.ac.uk/pdbsum/9nxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9nxy 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 ==
SARS-CoV-2 initiates infection of host cells by fusing its envelope lipid bilayer with the cell membrane. To overcome kinetic barriers for membrane fusion, the virus-encoded spike (S) protein refolds from a metastable prefusion state to a lower energy, stable postfusion conformation. The protein is first split into S1 and S2 fragments at a proteolytic site after synthesis, and presumably further cleaved at a second site, known as the S2' site, before membrane fusion can occur. Here, we report a cryo-EM structure of S2 fragment after the S2' cleavage, possibly representing a late fusion intermediate conformation, in which the fusion peptide and transmembrane segment have yet to pack together, distinct from the final, postfusion state. Functional assays demonstrate that the S2' cleavage accelerates membrane fusion, probably by stabilizing membrane fusion intermediates. These results advance our understanding of SARS-CoV-2 entry and may guide intervention strategies against pathogenetic coronaviruses.

Effect of the S2' site cleavage on SARS-CoV-2 spike.,Shi W, Jonaid GM, Kibria MG, Allen J, Peng H, Rits-Volloch S, Zhu H, Wang S, Walsh RM, Lu J, Chen B Nat Commun. 2025 Nov 27;16(1):11675. doi: 10.1038/s41467-025-66693-w. PMID:41309650<ref>PMID:41309650</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 9nxy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Chen B]]
[[Category: Jonaid G]]
[[Category: Shi W]]