7t9k

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(New page: ==== <StructureSection load='7t9k' size='340' side='right'caption='7t9k' scene=''> == Structural highlights == <table><tr><td colspan='2'>Full crystallographic information is availabl...)
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==Cryo-EM structure of SARS-CoV-2 Omicron spike protein in complex with human ACE2==
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<StructureSection load='7t9k' size='340' side='right'caption='[[7t9k]]' scene=''>
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<StructureSection load='7t9k' size='340' side='right'caption='[[7t9k]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7t9k]] is a 5 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=7T9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T9K FirstGlance]. <br>
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</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=7t9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t9k OCA], [https://pdbe.org/7t9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t9k RCSB], [https://www.ebi.ac.uk/pdbsum/7t9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t9k ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7t9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t9k OCA], [https://pdbe.org/7t9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t9k RCSB], [https://www.ebi.ac.uk/pdbsum/7t9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t9k ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The newly reported Omicron variant is poised to replace Delta as the most prevalent SARS-CoV-2 variant across the world. Cryo-EM structural analysis of the Omicron variant spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 and R498 in the RBD with ACE2. These interactions appear to compensate for other Omicron mutations such as K417N known to reduce ACE2 binding affinity, resulting in similar biochemical ACE2 binding affinities for Delta and Omicron variants. Neutralization assays show that pseudoviruses displaying the Omicron spike protein exhibit increased antibody evasion. The increase in antibody evasion, together with retention of strong interactions at the ACE2 interface, thus represent important molecular features that likely contribute to the rapid spread of the Omicron variant.
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SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein-ACE2 complex.,Mannar D, Saville JW, Zhu X, Srivastava SS, Berezuk AM, Tuttle KS, Marquez AC, Sekirov I, Subramaniam S Science. 2022 Feb 18;375(6582):760-764. doi: 10.1126/science.abn7760. Epub 2022, Jan 20. PMID:35050643<ref>PMID:35050643</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7t9k" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]]
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*[[Spike protein 3D structures|Spike protein 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Severe acute respiratory syndrome coronavirus 2]]
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[[Category: Berezuk AM]]
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[[Category: Mannar D]]
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[[Category: Saville JW]]
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[[Category: Srivastava SS]]
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[[Category: Subramaniam S]]
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[[Category: Tuttle KS]]
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[[Category: Zhu X]]

Current revision

Cryo-EM structure of SARS-CoV-2 Omicron spike protein in complex with human ACE2

PDB ID 7t9k

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