OCA at 19:52, 7 September 2022

OCA — Wed, 07 Sep 2022 19:52:08 GMT

←Older revision		Revision as of 19:52, 7 September 2022
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-	====	+	==Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-3152 Fab==
-	<StructureSection load='7wr8' size='340' side='right'caption='[[7wr8]]' scene=''>	+	<StructureSection load='7wr8' size='340' side='right'caption='[[7wr8]], [[Resolution\|resolution]] 3.50Å' 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'>[[7wr8]] is a 3 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=7WR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WR8 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=7wr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wr8 OCA], [https://pdbe.org/7wr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wr8 RCSB], [https://www.ebi.ac.uk/pdbsum/7wr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wr8 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=FUC:ALPHA-L-FUCOSE'>FUC</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=7wr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wr8 OCA], [https://pdbe.org/7wr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wr8 RCSB], [https://www.ebi.ac.uk/pdbsum/7wr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wr8 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 ==
		+	SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.2(1). The new variants' receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles(2), epitope distribution(3) and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes. However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab(4) and Cilgavimab(5) can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
		+
		+	BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection.,Cao Y, Yisimayi A, Jian F, Song W, Xiao T, Wang L, Du S, Wang J, Li Q, Chen X, Yu Y, Wang P, Zhang Z, Liu P, An R, Hao X, Wang Y, Wang J, Feng R, Sun H, Zhao L, Zhang W, Zhao D, Zheng J, Yu L, Li C, Zhang N, Wang R, Niu X, Yang S, Song X, Chai Y, Hu Y, Shi Y, Zheng L, Li Z, Gu Q, Shao F, Huang W, Jin R, Shen Z, Wang Y, Wang X, Xiao J, Xie XS Nature. 2022 Jun 17. pii: 10.1038/s41586-022-04980-y. doi:, 10.1038/s41586-022-04980-y. PMID:35714668<ref>PMID:35714668</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7wr8" style="background-color:#fffaf0;"></div>
		+	== 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: Du S]]
		+	[[Category: Xiao JY]]

OCA at 09:47, 22 June 2022

OCA — Wed, 22 Jun 2022 09:47:21 GMT

←Older revision		Revision as of 09:47, 22 June 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7wr8 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7wr8' size='340' side='right'caption='[[7wr8]]' scene=''>
-	~~Authors~~: ~~Du, S~~.~~, Xiao, J~~.Y.	+	== 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~~: ~~Local CryoEM structure of the SARS-CoV-2 S6P(B~~.1.1.~~529) in complex with BD55~~-~~3152 Fab~~	+	</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=7wr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wr8 OCA], [https://pdbe.org/7wr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wr8 RCSB], [https://www.ebi.ac.uk/pdbsum/7wr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wr8 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Du, S~~]]	+	__TOC__
-	[[Category: ~~Xiao, J.Y~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:01, 9 March 2022

OCA — Wed, 09 Mar 2022 05:01:58 GMT

←Older revision		Revision as of 05:01, 9 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7wr8 is ON HOLD	+	The entry 7wr8 is ON HOLD until Paper Publication

	Authors: Du, S., Xiao, J.Y.		Authors: Du, S., Xiao, J.Y.

OCA: Protected "7wr8" [edit=sysop:move=sysop]

OCA — Wed, 02 Feb 2022 05:52:11 GMT

Protected "7wr8" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:52, 2 February 2022

OCA: New page: '''Unreleased structure''' The entry 7wr8 is ON HOLD Authors: Du, S., Xiao, J.Y. Description: Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-3152 Fab [[Ca...

OCA — Wed, 02 Feb 2022 05:52:10 GMT

New page: '''Unreleased structure''' The entry 7wr8 is ON HOLD Authors: Du, S., Xiao, J.Y. Description: Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-3152 Fab [[Ca...

New page

'''Unreleased structure'''

The entry 7wr8 is ON HOLD

Authors: Du, S., Xiao, J.Y.

Description: Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-3152 Fab
[[Category: Unreleased Structures]]
[[Category: Du, S]]
[[Category: Xiao, J.Y]]

7wr8 - Revision history

OCA at 19:52, 7 September 2022

OCA at 09:47, 22 June 2022

OCA at 05:01, 9 March 2022

OCA: Protected "7wr8" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7wr8 is ON HOLD Authors: Du, S., Xiao, J.Y. Description: Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-3152 Fab [[Ca...