7tex
From Proteopedia
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| - | ==== | + | ==Cryo-EM structure of SARS-CoV-2 Delta (B.1.617.2) spike protein in complex with human ACE2== |
| - | <StructureSection load='7tex' size='340' side='right'caption='[[7tex]]' scene=''> | + | <StructureSection load='7tex' size='340' side='right'caption='[[7tex]], [[Resolution|resolution]] 3.27Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7tex]] 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=7TEX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TEX 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=7tex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tex OCA], [https://pdbe.org/7tex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tex RCSB], [https://www.ebi.ac.uk/pdbsum/7tex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tex ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.27Å</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=7tex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tex OCA], [https://pdbe.org/7tex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tex RCSB], [https://www.ebi.ac.uk/pdbsum/7tex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tex 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 == | ||
| + | The Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this study, we assess structural and biochemical aspects of viral fitness for these two variants using cryo-electron microscopy (cryo-EM), ACE2-binding and antibody neutralization analyses. Both variants demonstrate escape of antibodies targeting the N-terminal domain, an important immune hotspot for neutralizing epitopes. Compared to wild-type and Kappa lineages, Delta variant spike proteins show modest increase in ACE2 affinity, likely due to enhanced electrostatic complementarity at the RBD-ACE2 interface, which we characterize by cryo-EM. Unexpectedly, Kappa variant spike trimers form a structural head-to-head dimer-of-trimers assembly, which we demonstrate is a result of the E484Q mutation and with unknown biological implications. The combination of increased antibody escape and enhanced ACE2 binding provides an explanation, in part, for the rapid global dominance of the Delta variant. | ||
| + | |||
| + | Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants.,Saville JW, Mannar D, Zhu X, Srivastava SS, Berezuk AM, Demers JP, Zhou S, Tuttle KS, Sekirov I, Kim A, Li W, Dimitrov DS, Subramaniam S Nat Commun. 2022 Feb 8;13(1):742. doi: 10.1038/s41467-022-28324-6. PMID:35136050<ref>PMID:35136050</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7tex" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]] | ||
| + | *[[Spike protein 3D structures|Spike protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Severe acute respiratory syndrome coronavirus 2]] |
| + | [[Category: Berezuk AM]] | ||
| + | [[Category: Demers JP]] | ||
| + | [[Category: Mannar D]] | ||
| + | [[Category: Saville JW]] | ||
| + | [[Category: Srivastava SS]] | ||
| + | [[Category: Subramaniam S]] | ||
| + | [[Category: Tuttle KS]] | ||
| + | [[Category: Zhou S]] | ||
| + | [[Category: Zhu X]] | ||
Current revision
Cryo-EM structure of SARS-CoV-2 Delta (B.1.617.2) spike protein in complex with human ACE2
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