7ya1: Difference between revisions
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==== | ==Cryo-EM structure of hACE2-bound SARS-CoV-2 Omicron spike protein with L371S, P373S and F375S mutations (local refinement)== | ||
<StructureSection load='7ya1' size='340' side='right'caption='[[7ya1]]' scene=''> | <StructureSection load='7ya1' size='340' side='right'caption='[[7ya1]], [[Resolution|resolution]] 3.11Å' 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'>[[7ya1]] is a 2 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=7YA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YA1 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=7ya1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ya1 OCA], [https://pdbe.org/7ya1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ya1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ya1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ya1 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]] 3.11Å</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>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7ya1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ya1 OCA], [https://pdbe.org/7ya1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ya1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ya1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ya1 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses on apo Omicron spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs). Furthermore, we found that S371L, S373P and S375F substitutions enhance the stability of the one-RBD-up conformation to prevent exposing more up-RBDs triggered by ACE2 binding. The increased stability of the one-RBD-up conformation restricts the accessibility of S304 NAb, which targets a cryptic epitope in the closed conformation, thus facilitating the immune evasion by Omicron. These results expand our understanding of Omicron spike's conformation, receptor binding and antibody evasion mechanism. | |||
Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape.,Zhao Z, Zhou J, Tian M, Huang M, Liu S, Xie Y, Han P, Bai C, Han P, Zheng A, Fu L, Gao Y, Peng Q, Li Y, Chai Y, Zhang Z, Zhao X, Song H, Qi J, Wang Q, Wang P, Gao GF Nat Commun. 2022 Aug 24;13(1):4958. doi: 10.1038/s41467-022-32665-7. PMID:36002453<ref>PMID:36002453</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ya1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[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: Gao GF]] | |||
[[Category: Qi JX]] | |||
[[Category: Xie YF]] | |||
[[Category: Zhao ZN]] | |||
Latest revision as of 14:46, 23 October 2024
Cryo-EM structure of hACE2-bound SARS-CoV-2 Omicron spike protein with L371S, P373S and F375S mutations (local refinement)Cryo-EM structure of hACE2-bound SARS-CoV-2 Omicron spike protein with L371S, P373S and F375S mutations (local refinement)
Structural highlights
FunctionACE2_HUMAN Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.[1] [2] [3] Publication Abstract from PubMedOmicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses on apo Omicron spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs). Furthermore, we found that S371L, S373P and S375F substitutions enhance the stability of the one-RBD-up conformation to prevent exposing more up-RBDs triggered by ACE2 binding. The increased stability of the one-RBD-up conformation restricts the accessibility of S304 NAb, which targets a cryptic epitope in the closed conformation, thus facilitating the immune evasion by Omicron. These results expand our understanding of Omicron spike's conformation, receptor binding and antibody evasion mechanism. Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape.,Zhao Z, Zhou J, Tian M, Huang M, Liu S, Xie Y, Han P, Bai C, Han P, Zheng A, Fu L, Gao Y, Peng Q, Li Y, Chai Y, Zhang Z, Zhao X, Song H, Qi J, Wang Q, Wang P, Gao GF Nat Commun. 2022 Aug 24;13(1):4958. doi: 10.1038/s41467-022-32665-7. PMID:36002453[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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