7qti - Revision history

OCA at 18:56, 7 September 2022

2022-09-07T18:56:51Z

←Older revision		Revision as of 18:56, 7 September 2022
Line 9:		Line 9:
	== Function ==		== 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][[https://www.uniprot.org/uniprot/M1E1E4_9HIV1 M1E1E4_9HIV1]]		[[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][[https://www.uniprot.org/uniprot/M1E1E4_9HIV1 M1E1E4_9HIV1]]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The SARS-CoV-2 Omicron variant has very high levels of transmission, is resistant to neutralization by authorized therapeutic human monoclonal antibodies (mAb) and is less sensitive to vaccine-mediated immunity. To provide additional therapies against Omicron, we isolated a mAb named P2G3 from a previously infected vaccinated donor and showed that it has picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other variants tested. We solved the structure of P2G3 Fab in complex with the Omicron spike using cryo-electron microscopy at 3.04 A resolution to identify the P2G3 epitope as a Class 3 mAb that is different from mAb-binding spike epitopes reported previously. Using a SARS-CoV-2 Omicron monkey challenge model, we show that P2G3 alone, or in combination with P5C3 (a broadly active Class 1 mAb previously identified), confers complete prophylactic or therapeutic protection. Although we could select for SARS-CoV-2 mutants escaping neutralization by P2G3 or by P5C3 in vitro, they had low infectivity and 'escape' mutations are extremely rare in public sequence databases. We conclude that this combination of mAbs has potential as an anti-Omicron drug.
		+
		+	Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys.,Fenwick C, Turelli P, Ni D, Perez L, Lau K, Herate C, Marlin R, Lana E, Pellaton C, Raclot C, Esteves-Leuenberger L, Campos J, Farina A, Fiscalini F, Dereuddre-Bosquet N, Relouzat F, Abdelnabi R, Foo CS, Neyts J, Leyssen P, Levy Y, Pojer F, Stahlberg H, LeGrand R, Trono D, Pantaleo G Nat Microbiol. 2022 Sep;7(9):1376-1389. doi: 10.1038/s41564-022-01198-6. Epub, 2022 Jul 25. PMID:35879526<ref>PMID:35879526</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7qti" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:48, 7 September 2022

2022-09-07T16:48:26Z

←Older revision		Revision as of 16:48, 7 September 2022
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-	====	+	==SARS-CoV-2 S Omicron Spike B.1.1.529 - 3-P2G3 and 1-P5C3 Fabs (Global)==
-	<StructureSection load='7qti' size='340' side='right'caption='[[7qti]]' scene=''>	+	<StructureSection load='7qti' size='340' side='right'caption='[[7qti]], [[Resolution\|resolution]] 3.04Å' 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'>[[7qti]] is a 11 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=7QTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QTI 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=7qti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qti OCA], [https://pdbe.org/7qti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qti RCSB], [https://www.ebi.ac.uk/pdbsum/7qti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qti 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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=7qti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qti OCA], [https://pdbe.org/7qti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qti RCSB], [https://www.ebi.ac.uk/pdbsum/7qti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qti 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][[https://www.uniprot.org/uniprot/M1E1E4_9HIV1 M1E1E4_9HIV1]]
		+	== 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: Fenwick C]]
		+	[[Category: Lau K]]
		+	[[Category: Ni D]]
		+	[[Category: Pantaleo G]]
		+	[[Category: Perez L]]
		+	[[Category: Pojer F]]
		+	[[Category: Stahlberg H]]
		+	[[Category: Trono D]]
		+	[[Category: Turelli P]]

OCA at 04:51, 3 August 2022

2022-08-03T04:51:51Z

←Older revision		Revision as of 04:51, 3 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7qti ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7qti' size='340' side='right'caption='[[7qti]]' scene=''>
-	~~Authors~~:	+	== 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~~:	+	</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=7qti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qti OCA], [https://pdbe.org/7qti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qti RCSB], [https://www.ebi.ac.uk/pdbsum/7qti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qti ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 10:20, 27 April 2022

2022-04-27T10:20:18Z

←Older revision		Revision as of 10:20, 27 April 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

2022-01-27T05:20:38Z

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

←Older revision

Revision as of 05:20, 27 January 2022

OCA: New page: '''Unreleased structure''' The entry 7qti is ON HOLD Authors: Description: Category: Unreleased Structures

2022-01-27T05:20:37Z

New page: '''Unreleased structure''' The entry 7qti is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7qti is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]