7tp2: Difference between revisions
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==Delta (B.1.617.2) SARS-CoV-2 variant spike protein (S-GSAS-Delta) in the 3-RBD-down conformation; Subclassification D10 state== | ==Delta (B.1.617.2) SARS-CoV-2 variant spike protein (S-GSAS-Delta) in the 3-RBD-down conformation; Subclassification D10 state== | ||
<StructureSection load='7tp2' size='340' side='right'caption='[[7tp2]]' scene=''> | <StructureSection load='7tp2' size='340' side='right'caption='[[7tp2]], [[Resolution|resolution]] 3.72Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TP2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7tp2]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TP2 FirstGlance]. <br> | ||
</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=7tp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tp2 OCA], [https://pdbe.org/7tp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tp2 RCSB], [https://www.ebi.ac.uk/pdbsum/7tp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tp2 ProSAT]</span></td></tr> | </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=7tp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tp2 OCA], [https://pdbe.org/7tp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tp2 RCSB], [https://www.ebi.ac.uk/pdbsum/7tp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tp2 ProSAT]</span></td></tr> | |||
</table> | </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 == | |||
Aided by extensive spike protein mutation, the SARS-CoV-2 Omicron variant overtook the previously dominant Delta variant. Spike conformation plays an essential role in SARS-CoV-2 evolution via changes in receptor binding domain (RBD) and neutralizing antibody epitope presentation affecting virus transmissibility and immune evasion. Here, we determine cryo-EM structures of the Omicron and Delta spikes to understand the conformational impacts of mutations in each. The Omicron spike structure revealed an unusually tightly packed RBD organization with long range impacts that were not observed in the Delta spike. Binding and crystallography revealed increased flexibility at the functionally critical fusion peptide site in the Omicron spike. These results reveal a highly evolved Omicron spike architecture with possible impacts on its high levels of immune evasion and transmissibility. | |||
Structural diversity of the SARS-CoV-2 Omicron spike.,Gobeil SM, Henderson R, Stalls V, Janowska K, Huang X, May A, Speakman M, Beaudoin E, Manne K, Li D, Parks R, Barr M, Deyton M, Martin M, Mansouri K, Edwards RJ, Sempowski GD, Saunders KO, Wiehe K, Williams W, Korber B, Haynes BF, Acharya P bioRxiv. 2022 Jan 26. doi: 10.1101/2022.01.25.477784. PMID:35118469<ref>PMID:35118469</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7tp2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Acharya P]] | [[Category: Acharya, P]] | ||
[[Category: Gobeil S]] | [[Category: Gobeil, S]] | ||
[[Category: Sars-cov-2 spike protein trimer]] | |||
[[Category: Viral protein]] | |||
Revision as of 14:11, 16 February 2022
Delta (B.1.617.2) SARS-CoV-2 variant spike protein (S-GSAS-Delta) in the 3-RBD-down conformation; Subclassification D10 stateDelta (B.1.617.2) SARS-CoV-2 variant spike protein (S-GSAS-Delta) in the 3-RBD-down conformation; Subclassification D10 state
Structural highlights
Function[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][1] [2] [3] 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] Publication Abstract from PubMedAided by extensive spike protein mutation, the SARS-CoV-2 Omicron variant overtook the previously dominant Delta variant. Spike conformation plays an essential role in SARS-CoV-2 evolution via changes in receptor binding domain (RBD) and neutralizing antibody epitope presentation affecting virus transmissibility and immune evasion. Here, we determine cryo-EM structures of the Omicron and Delta spikes to understand the conformational impacts of mutations in each. The Omicron spike structure revealed an unusually tightly packed RBD organization with long range impacts that were not observed in the Delta spike. Binding and crystallography revealed increased flexibility at the functionally critical fusion peptide site in the Omicron spike. These results reveal a highly evolved Omicron spike architecture with possible impacts on its high levels of immune evasion and transmissibility. Structural diversity of the SARS-CoV-2 Omicron spike.,Gobeil SM, Henderson R, Stalls V, Janowska K, Huang X, May A, Speakman M, Beaudoin E, Manne K, Li D, Parks R, Barr M, Deyton M, Martin M, Mansouri K, Edwards RJ, Sempowski GD, Saunders KO, Wiehe K, Williams W, Korber B, Haynes BF, Acharya P bioRxiv. 2022 Jan 26. doi: 10.1101/2022.01.25.477784. PMID:35118469[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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