OCA at 10:51, 31 March 2021

OCA — Wed, 31 Mar 2021 10:51:09 GMT

←Older revision		Revision as of 10:51, 31 March 2021
Line 1:		Line 1:

	==SARS-CoV-2 D614G 3-RBD-down Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-D614G Sub-Classification)==		==SARS-CoV-2 D614G 3-RBD-down Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-D614G Sub-Classification)==
-	<StructureSection load='7ke7' size='340' side='right'caption='[[7ke7]]' scene=''>	+	<StructureSection load='7ke7' size='340' side='right'caption='[[7ke7]], [[Resolution\|resolution]] 3.32Å' 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=7KE7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7KE7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ke7]] 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=7KE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KE7 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7ke7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ke7 OCA], [~~http~~://pdbe.org/7ke7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7ke7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7ke7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7ke7 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=7ke7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ke7 OCA], [https://pdbe.org/7ke7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ke7 RCSB], [https://www.ebi.ac.uk/pdbsum/7ke7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ke7 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 ==
		+	The severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein is the target of vaccine design efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic and are now the dominant form worldwide. Here, we explore S conformational changes and the effects of the D614G mutation on a soluble S ectodomain construct. Cryoelectron microscopy (cryo-EM) structures reveal altered receptor binding domain (RBD) disposition; antigenicity and proteolysis experiments reveal structural changes and enhanced furin cleavage efficiency of the G614 variant. Furthermore, furin cleavage alters the up/down ratio of the RBDs in the G614 S ectodomain, demonstrating an allosteric effect on RBD positioning triggered by changes in the SD2 region, which harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 S conformational landscape and allostery and have implications for vaccine design.
		+
		+	D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction.,Gobeil SM, Janowska K, McDowell S, Mansouri K, Parks R, Manne K, Stalls V, Kopp MF, Henderson R, Edwards RJ, Haynes BF, Acharya P Cell Rep. 2021 Jan 12;34(2):108630. doi: 10.1016/j.celrep.2020.108630. Epub 2020 , Dec 26. PMID:33417835<ref>PMID:33417835</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7ke7" 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 07:27, 4 November 2020

OCA — Wed, 04 Nov 2020 07:27:26 GMT

←Older revision		Revision as of 07:27, 4 November 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7ke7 is ON HOLD~~	+	==SARS-CoV-2 D614G 3-RBD-down Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-D614G Sub-Classification)==
-		+	<StructureSection load='7ke7' size='340' side='right'caption='[[7ke7]]' 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=7KE7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KE7 FirstGlance]. <br>
-	~~Description:~~ SARS-CoV-2 D614G 3-RBD-down Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-D614G Sub-Classification)	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7ke7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ke7 OCA], [http://pdbe.org/7ke7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7ke7 RCSB], [http://www.ebi.ac.uk/pdbsum/7ke7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7ke7 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Gobeil~~, S]]	+	__TOC__
-	[[Category: Acharya, P]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Acharya P]]
		+	[[Category: Gobeil S]]

OCA: Protected "7ke7" [edit=sysop:move=sysop]

OCA — Wed, 21 Oct 2020 06:52:00 GMT

Protected "7ke7" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:52, 21 October 2020

OCA: New page: '''Unreleased structure''' The entry 7ke7 is ON HOLD Authors: Gobeil, S., Acharya, P. Description: SARS-CoV-2 D614G 3-RBD-down Spike Protein Trimer without the P986-P987 stabilizing mu...

OCA — Wed, 21 Oct 2020 06:51:59 GMT

New page: '''Unreleased structure''' The entry 7ke7 is ON HOLD Authors: Gobeil, S., Acharya, P. Description: SARS-CoV-2 D614G 3-RBD-down Spike Protein Trimer without the P986-P987 stabilizing mu...

New page

'''Unreleased structure'''

The entry 7ke7 is ON HOLD

Authors: Gobeil, S., Acharya, P.

Description: SARS-CoV-2 D614G 3-RBD-down Spike Protein Trimer without the P986-P987 stabilizing mutations (S-GSAS-D614G Sub-Classification)
[[Category: Unreleased Structures]]
[[Category: Gobeil, S]]
[[Category: Acharya, P]]

7ke7 - Revision history

OCA at 10:51, 31 March 2021

OCA at 07:27, 4 November 2020

OCA: Protected "7ke7" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7ke7 is ON HOLD Authors: Gobeil, S., Acharya, P. Description: SARS-CoV-2 D614G 3-RBD-down Spike Protein Trimer without the P986-P987 stabilizing mu...