View source for 7sxx


==Cryo-EM structure of the SARS-CoV-2 D614G mutant spike protein ectodomain bound to human ACE2 ectodomain (global refinement)==
<StructureSection load='7sxx' size='340' side='right'caption='[[7sxx]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sxx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7SXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SXX 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]] 2.66&#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=7sxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sxx OCA], [https://pdbe.org/7sxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sxx RCSB], [https://www.ebi.ac.uk/pdbsum/7sxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sxx 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 recently emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Beta (B.1.351) and Gamma (P.1) variants of concern (VoCs) include a key mutation (N501Y) found in the Alpha (B.1.1.7) variant that enhances affinity of the spike protein for its receptor, angiotensin-converting enzyme 2 (ACE2). Additional mutations are found in these variants at residues 417 and 484 that appear to promote antibody evasion. In contrast, the Epsilon variants (B.1.427/429) lack the N501Y mutation yet exhibit antibody evasion. We have engineered spike proteins to express these receptor binding domain (RBD) VoC mutations either in isolation or in different combinations and analyze the effects using biochemical assays and cryoelectron microscopy (cryo-EM) structural analyses. Overall, our findings suggest that the emergence of new SARS-CoV-2 variant spikes can be rationalized as the result of mutations that confer increased ACE2 affinity, increased antibody evasion, or both, providing a framework to dissect the molecular factors that drive VoC evolution.

Structural analysis of receptor binding domain mutations in SARS-CoV-2 variants of concern that modulate ACE2 and antibody binding.,Mannar D, Saville JW, Zhu X, Srivastava SS, Berezuk AM, Zhou S, Tuttle KS, Kim A, Li W, Dimitrov DS, Subramaniam S Cell Rep. 2021 Dec 21;37(12):110156. doi: 10.1016/j.celrep.2021.110156. Epub 2021, Dec 4. PMID:34914928<ref>PMID:34914928</ref>

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

==See Also==
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Berezuk AM]]
[[Category: Dimitrov DS]]
[[Category: Kim A]]
[[Category: Li W]]
[[Category: Mannar D]]
[[Category: Saville JW]]
[[Category: Srivastava SS]]
[[Category: Subramaniam S]]
[[Category: Tuttle KS]]
[[Category: Zhou S]]
[[Category: Zhu X]]