View source for 6xra


==Distinct conformational states of SARS-CoV-2 spike protein==
<StructureSection load='6xra' size='340' side='right'caption='[[6xra]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xra]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XRA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XRA FirstGlance]. <br>
</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xra FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xra OCA], [http://pdbe.org/6xra PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xra RCSB], [http://www.ebi.ac.uk/pdbsum/6xra PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xra ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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 ==
Intervention strategies are urgently needed to control the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here we report two cryo-EM structures, derived from a preparation of the full-length S protein, representing its prefusion (2.9A resolution) and postfusion (3.0A resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains clamped down by a segment adjacent to the fusion peptide. The postfusion structure is strategically decorated by N-linked glycans, suggesting possible protective roles against host immune responses and harsh external conditions. These findings advance our understanding of SARS-CoV-2 entry and may guide development of vaccines and therapeutics.

Distinct conformational states of SARS-CoV-2 spike protein.,Cai Y, Zhang J, Xiao T, Peng H, Sterling SM, Walsh RM Jr, Rawson S, Rits-Volloch S, Chen B Science. 2020 Jul 21. pii: science.abd4251. doi: 10.1126/science.abd4251. PMID:32694201<ref>PMID:32694201</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xra" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: 2019-ncov]]
[[Category: Large Structures]]
[[Category: Cai, Y F]]
[[Category: Chen, B]]
[[Category: Jr, R M.Walsh]]
[[Category: Peng, H Q]]
[[Category: Rawson, S]]
[[Category: Rits-Volloch, S]]
[[Category: Sterling, S M]]
[[Category: Xiao, T S]]
[[Category: Zhang, J]]
[[Category: Viral protein]]