View source for 6vxx


==Structure of the SARS-CoV-2 spike glycoprotein (closed state)==
<SX load='6vxx' size='340' side='right' viewer='molstar' caption='[[6vxx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vxx]] 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=6VXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VXX 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]] 2.8&#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=6vxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vxx OCA], [https://pdbe.org/6vxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vxx RCSB], [https://www.ebi.ac.uk/pdbsum/6vxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vxx 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 ==
The emergence of SARS-CoV-2 has resulted in &gt;90,000 infections and &gt;3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.,Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D Cell. 2020 Mar 6. pii: S0092-8674(20)30262-2. doi: 10.1016/j.cell.2020.02.058. PMID:32155444<ref>PMID:32155444</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 6vxx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sandbox 3001|Sandbox 3001]]
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
<references/>
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[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: McGuire AT]]
[[Category: Park YJ]]
[[Category: Tortorici MA]]
[[Category: Veesler D]]
[[Category: Wall A]]
[[Category: Walls AC]]