7lyq - Revision history

OCA at 08:29, 7 December 2022

2022-12-07T08:29:34Z

←Older revision		Revision as of 08:29, 7 December 2022
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	<StructureSection load='7lyq' size='340' side='right'caption='[[7lyq]], [[Resolution\|resolution]] 3.34Å' scene=''>		<StructureSection load='7lyq' size='340' side='right'caption='[[7lyq]], [[Resolution\|resolution]] 3.34Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7lyq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~2019-ncov 2019-ncov~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lyq]] is a 3 chain structure with sequence from [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=7LYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYQ FirstGlance]. <br>
	</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>		</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S, 2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</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=7lyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lyq OCA], [https://pdbe.org/7lyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lyq RCSB], [https://www.ebi.ac.uk/pdbsum/7lyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lyq ProSAT]</span></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=7lyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lyq OCA], [https://pdbe.org/7lyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lyq RCSB], [https://www.ebi.ac.uk/pdbsum/7lyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lyq ProSAT]</span></td></tr>
	</table>		</table>
	== 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/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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~New~~ SARS-CoV-2 variants ~~that have accumulated~~ multiple mutations ~~in the spike (S) glycoprotein~~ enable increased transmission and resistance ~~to neutralizing antibodies~~. Here, we study ~~the antigenic and structural impacts of the S protein mutations from four variants~~, one that was involved in transmission between minks and humans, and ~~three~~ that ~~rapidly~~ spread in human populations ~~and originated in the United Kingdom, Brazil or South Africa~~. All variants ~~either retained or improved~~ binding to the ~~ACE2 receptor. The~~ B.1.1.7 (UK) and B.1.1.28 (Brazil) ~~spike variants showed reduced binding to neutralizing NTD~~ and ~~RBD antibodies, respectively, while the~~ B.1.351 (SA) ~~variant showed reduced binding~~ to ~~both NTD- and RBD-directed~~ antibodies. ~~Cryo-EM structural analyses~~ revealed allosteric effects of ~~the~~ mutations ~~on spike conformations~~ and ~~revealed~~ mechanistic differences that either ~~drive~~ inter-species transmission or ~~promotes viral~~ escape from dominant neutralizing epitopes. Highlights: Cryo-EM structures reveal changes in SARS-CoV-2 S protein during inter-species transmission or immune evasion.Adaptation to mink resulted in increased ACE2 binding and spike destabilization.B.1.1.7 S mutations reveal an intricate balance of stabilizing and destabilizing effects that impact receptor and antibody binding.E484K mutation in B.1.351 and B.1.1.28 S proteins drives immune evasion by altering RBD conformation.S protein uses different mechanisms to converge upon similar solutions for altering RBD up/down positioning.	+	SARS-CoV-2 variants with multiple spike mutations enable increased transmission and antibody resistance. Here, we combine cryo-EM, binding and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased ACE2 receptor binding and increased propensity for RBD up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either inter-species transmission or escape from antibody neutralization.

-	Effect of natural mutations of SARS-CoV-2 on spike structure, conformation and antigenicity.,Gobeil SM, Janowska K, McDowell S, Mansouri K, Parks R, Stalls V, Kopp MF, Manne K, ~~Saunders~~ K, Edwards RJ, Haynes BF, Henderson RC, Acharya P ~~bioRxiv~~. 2021 ~~Mar 15~~. doi: 10.~~1101~~/~~2021.03.11~~.~~435037~~. PMID:~~33758838~~<ref>PMID:~~33758838~~</ref>	+	Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.,Gobeil SM, Janowska K, McDowell S, Mansouri K, Parks R, Stalls V, Kopp MF, Manne K, Li D, Wiehe K, Saunders KO, Edwards RJ, Korber B, Haynes BF, Henderson R, Acharya P Science. 2021 Jun 24. pii: science.abi6226. doi: 10.1126/science.abi6226. PMID:34168071<ref>PMID:34168071</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Acharya, P~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
-	[[Category: ~~Gobeil, S~~]]	+	[[Category: Acharya P]]
-	[[Category: ~~Sars-cov-2 spike protein trimer]]~~	+	[[Category: Gobeil S]]
-	~~[[Category: Viral protein~~]]	+

OCA at 07:16, 7 April 2021

2021-04-07T07:16:15Z

←Older revision		Revision as of 07:16, 7 April 2021
Line 1:		Line 1:

	==South African (B.1.351) SARS-CoV-2 spike protein variant (S-GSAS-B.1.351) in the 1-RBD-up conformation==		==South African (B.1.351) SARS-CoV-2 spike protein variant (S-GSAS-B.1.351) in the 1-RBD-up conformation==
-	<StructureSection load='7lyq' size='340' side='right'caption='[[7lyq]]' scene=''>	+	<StructureSection load='7lyq' size='340' side='right'caption='[[7lyq]], [[Resolution\|resolution]] 3.34Å' 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=7LYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lyq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYQ 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=7lyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lyq OCA], [https://pdbe.org/7lyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lyq RCSB], [https://www.ebi.ac.uk/pdbsum/7lyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lyq 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S, 2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</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=7lyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lyq OCA], [https://pdbe.org/7lyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lyq RCSB], [https://www.ebi.ac.uk/pdbsum/7lyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lyq 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 ==
		+	New SARS-CoV-2 variants that have accumulated multiple mutations in the spike (S) glycoprotein enable increased transmission and resistance to neutralizing antibodies. Here, we study the antigenic and structural impacts of the S protein mutations from four variants, one that was involved in transmission between minks and humans, and three that rapidly spread in human populations and originated in the United Kingdom, Brazil or South Africa. All variants either retained or improved binding to the ACE2 receptor. The B.1.1.7 (UK) and B.1.1.28 (Brazil) spike variants showed reduced binding to neutralizing NTD and RBD antibodies, respectively, while the B.1.351 (SA) variant showed reduced binding to both NTD- and RBD-directed antibodies. Cryo-EM structural analyses revealed allosteric effects of the mutations on spike conformations and revealed mechanistic differences that either drive inter-species transmission or promotes viral escape from dominant neutralizing epitopes. Highlights: Cryo-EM structures reveal changes in SARS-CoV-2 S protein during inter-species transmission or immune evasion.Adaptation to mink resulted in increased ACE2 binding and spike destabilization.B.1.1.7 S mutations reveal an intricate balance of stabilizing and destabilizing effects that impact receptor and antibody binding.E484K mutation in B.1.351 and B.1.1.28 S proteins drives immune evasion by altering RBD conformation.S protein uses different mechanisms to converge upon similar solutions for altering RBD up/down positioning.
		+
		+	Effect of natural mutations of SARS-CoV-2 on spike structure, conformation and antigenicity.,Gobeil SM, Janowska K, McDowell S, Mansouri K, Parks R, Stalls V, Kopp MF, Manne K, Saunders K, Edwards RJ, Haynes BF, Henderson RC, Acharya P bioRxiv. 2021 Mar 15. doi: 10.1101/2021.03.11.435037. PMID:33758838<ref>PMID:33758838</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lyq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Acharya P]]	+	[[Category: Acharya, P]]
-	[[Category: Gobeil S]]	+	[[Category: Gobeil, S]]
		+	[[Category: Sars-cov-2 spike protein trimer]]
		+	[[Category: Viral protein]]

OCA at 10:34, 31 March 2021

2021-03-31T10:34:27Z

←Older revision		Revision as of 10:34, 31 March 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7lyq is ON HOLD~~	+	==South African (B.1.351) SARS-CoV-2 spike protein variant (S-GSAS-B.1.351) in the 1-RBD-up conformation==
-		+	<StructureSection load='7lyq' size='340' side='right'caption='[[7lyq]]' scene=''>
-	~~Authors: Gobeil, S., Acharya, P.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYQ FirstGlance]. <br>
-	~~Description:~~ South African (B.1.351) SARS-CoV-2 spike protein variant (S-GSAS-B.1.351) in the 1-RBD-up conformation	+	</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=7lyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lyq OCA], [https://pdbe.org/7lyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lyq RCSB], [https://www.ebi.ac.uk/pdbsum/7lyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lyq ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Acharya, P]]	+	__TOC__
-	[[Category: Gobeil, S]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Acharya P]]
		+	[[Category: Gobeil S]]

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

2021-03-17T05:25:03Z

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

←Older revision

Revision as of 05:25, 17 March 2021

OCA: New page: '''Unreleased structure''' The entry 7lyq is ON HOLD Authors: Gobeil, S., Acharya, P. Description: South African (B.1.351) SARS-CoV-2 spike protein variant (S-GSAS-B.1.351) in the 1-RB...

2021-03-17T05:25:02Z

New page: '''Unreleased structure''' The entry 7lyq is ON HOLD Authors: Gobeil, S., Acharya, P. Description: South African (B.1.351) SARS-CoV-2 spike protein variant (S-GSAS-B.1.351) in the 1-RB...

New page

'''Unreleased structure'''

The entry 7lyq is ON HOLD

Authors: Gobeil, S., Acharya, P.

Description: South African (B.1.351) SARS-CoV-2 spike protein variant (S-GSAS-B.1.351) in the 1-RBD-up conformation
[[Category: Unreleased Structures]]
[[Category: Acharya, P]]
[[Category: Gobeil, S]]