OCA at 06:53, 21 November 2024

2024-11-21T06:53:39Z

← Older revision		Revision as of 06:53, 21 November 2024
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	====		==SARS-CoV-2 Omicron variant spike protein with two XGv347 binding to two open state RBDs==
	<StructureSection load='7web' size='340' side='right'caption='[[7web]]' scene=''>		<StructureSection load='7web' size='340' side='right'caption='[[7web]], [[Resolution\|resolution]] 3.70Å' 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'>[[7web]] is a 7 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=7WEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WEB 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=7web FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7web OCA], [https://pdbe.org/7web PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7web RCSB], [https://www.ebi.ac.uk/pdbsum/7web PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7web 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]] 3.7Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <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=7web FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7web OCA], [https://pdbe.org/7web PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7web RCSB], [https://www.ebi.ac.uk/pdbsum/7web PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7web 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 ==
			Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines(1,2). Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine.

			Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants.,Wang K, Jia Z, Bao L, Wang L, Cao L, Chi H, Hu Y, Li Q, Zhou Y, Jiang Y, Zhu Q, Deng Y, Liu P, Wang N, Wang L, Liu M, Li Y, Zhu B, Fan K, Fu W, Yang P, Pei X, Cui Z, Qin L, Ge P, Wu J, Liu S, Chen Y, Huang W, Wang Q, Qin CF, Wang Y, Qin C, Wang X Nature. 2022 Mar;603(7903):919-925. doi: 10.1038/s41586-022-04466-x. Epub 2022 , Jan 28. PMID:35090164<ref>PMID:35090164</ref>

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

			==See Also==
			*[[Antibody 3D structures\|Antibody 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: ~~Z-disk~~]]		[[Category: Severe acute respiratory syndrome coronavirus 2]]
			[[Category: Wang L]]
			[[Category: Wang X]]

OCA at 12:54, 4 May 2022

2022-05-04T12:54:41Z

← Older revision		Revision as of 12:54, 4 May 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7web ~~is ON HOLD~~		====
			<StructureSection load='7web' size='340' side='right'caption='[[7web]]' scene=''>
	~~Authors~~: ~~Wang, X~~.~~, Wang, L~~.		== 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>
	~~Description~~: ~~SARS~~-~~CoV-2 Omicron variant spike protein with two XGv347 binding to two open state RBDs~~		</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=7web FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7web OCA], [https://pdbe.org/7web PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7web RCSB], [https://www.ebi.ac.uk/pdbsum/7web PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7web ProSAT]</span></td></tr>
	[[~~Category~~: ~~Unreleased Structures~~]]		</table>
	[[Category: ~~Wang, L~~]]		__TOC__
	[[Category: ~~Wang, X~~]]		</StructureSection>
			[[Category: Large Structures]]
			[[Category: Z-disk]]

OCA: Protected "7web" [edit=sysop:move=sysop]

2021-12-29T12:43:21Z

Protected "7web" [edit=sysop:move=sysop]

← Older revision	Revision as of 12:43, 29 December 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7web is ON HOLD Authors: Wang, X., Wang, L. Description: SARS-CoV-2 Omicron variant spike protein with two XGv347 binding to two open state RBDs [[...

2021-12-29T12:43:20Z

New page: '''Unreleased structure''' The entry 7web is ON HOLD Authors: Wang, X., Wang, L. Description: SARS-CoV-2 Omicron variant spike protein with two XGv347 binding to two open state RBDs [[...

New page

'''Unreleased structure'''

The entry 7web is ON HOLD

Authors: Wang, X., Wang, L.

Description: SARS-CoV-2 Omicron variant spike protein with two XGv347 binding to two open state RBDs
[[Category: Unreleased Structures]]
[[Category: Wang, L]]
[[Category: Wang, X]]

7web - Revision history

OCA at 06:53, 21 November 2024

OCA at 12:54, 4 May 2022

OCA: Protected "7web" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7web is ON HOLD Authors: Wang, X., Wang, L. Description: SARS-CoV-2 Omicron variant spike protein with two XGv347 binding to two open state RBDs [[...