OCA at 11:35, 23 September 2020

OCA — Wed, 23 Sep 2020 11:35:05 GMT

←Older revision		Revision as of 11:35, 23 September 2020
Line 1:		Line 1:

	==Structure of the prefusion SARS-CoV-2 spike glycoprotein==		==Structure of the prefusion SARS-CoV-2 spike glycoprotein==
-	<StructureSection load='6z97' size='340' side='right'caption='[[6z97]]' scene=''>	+	<StructureSection load='6z97' size='340' side='right'caption='[[6z97]], [[Resolution\|resolution]] 3.40Å' 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=6Z97 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Z97 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6z97]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bpt4 Bpt4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z97 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Z97 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=6z97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z97 OCA], [http://pdbe.org/6z97 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6z97 RCSB], [http://www.ebi.ac.uk/pdbsum/6z97 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6z97 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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6yor\|6yor]], [[6yla\|6yla]], [[6ym0\|6ym0]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">wac ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10665 BPT4])</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=6z97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z97 OCA], [http://pdbe.org/6z97 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6z97 RCSB], [http://www.ebi.ac.uk/pdbsum/6z97 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6z97 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://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 ==
		+	There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 A of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.
		+
		+	Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike.,Huo J, Zhao Y, Ren J, Zhou D, Duyvesteyn HME, Ginn HM, Carrique L, Malinauskas T, Ruza RR, Shah PNM, Tan TK, Rijal P, Coombes N, Bewley KR, Tree JA, Radecke J, Paterson NG, Supasa P, Mongkolsapaya J, Screaton GR, Carroll M, Townsend A, Fry EE, Owens RJ, Stuart DI Cell Host Microbe. 2020 Jun 19. pii: S1931-3128(20)30351-6. doi:, 10.1016/j.chom.2020.06.010. PMID:32585135<ref>PMID:32585135</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6z97" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Fibritin\|Fibritin]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bpt4]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Carrique L]]	+	[[Category: Carrique, L]]
-	[[Category: Duyvesteyn ~~HME~~]]	+	[[Category: Duyvesteyn, H M.E]]
-	[[Category: Fry EE]]	+	[[Category: Fry, E E]]
-	[[Category: Huo J]]	+	[[Category: Huo, J]]
-	[[Category: Malinauskas T]]	+	[[Category: Malinauskas, T]]
-	[[Category: Owens R]]	+	[[Category: Owens, R]]
-	[[Category: Ren J]]	+	[[Category: Ren, J]]
-	[[Category: Ruza RR]]	+	[[Category: Ruza, R R]]
-	[[Category: Shah ~~PNM~~]]	+	[[Category: Shah, P N.M]]
-	[[Category: Stuart DI]]	+	[[Category: Stuart, D I]]
-	[[Category: Zhao Y]]	+	[[Category: Zhao, Y]]
-	[[Category: Zhou D]]	+	[[Category: Zhou, D]]
		+	[[Category: Complex]]
		+	[[Category: Cr3022]]
		+	[[Category: Rbd]]
		+	[[Category: Sars-cov-2 spike glycoprotein]]
		+	[[Category: Viral protein]]

OCA at 14:44, 8 July 2020

OCA — Wed, 08 Jul 2020 14:44:23 GMT

←Older revision		Revision as of 14:44, 8 July 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6z97 ~~is ON HOLD~~	+	==Structure of the prefusion SARS-CoV-2 spike glycoprotein==
-		+	<StructureSection load='6z97' size='340' side='right'caption='[[6z97]]' scene=''>
-	~~Authors~~: ~~Duyvesteyn, H~~.M.E.~~, Ren, J~~.~~, Zhao, Y~~.~~, Zhou, D~~.~~, Huo, J~~.~~, Carrique, L~~.~~, Malinauskas, T~~., ~~Ruza, R~~.R., ~~Shah~~, P.N.M., ~~Fry, E~~.E.~~, Owens, R~~., ~~Stuart, D~~.I.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z97 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Z97 FirstGlance]. <br>
-	~~Description: Structure of the prefusion SARS-CoV-2 spike glycoprotein~~	+	</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=6z97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z97 OCA], [http://pdbe.org/6z97 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6z97 RCSB], [http://www.ebi.ac.uk/pdbsum/6z97 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6z97 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Carrique, L]]	+	__TOC__
-	[[Category: ~~Ren, J~~]]	+	</StructureSection>
-	[[Category: ~~Shah, P.N.M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Malinauskas, T~~]]	+	[[Category: Carrique L]]
-	[[Category: ~~Duyvesteyn, H.M.E~~]]	+	[[Category: Duyvesteyn HME]]
-	[[Category: ~~Huo, J~~]]	+	[[Category: Fry EE]]
-	[[Category: ~~Zhao, Y~~]]	+	[[Category: Huo J]]
-	[[Category: ~~Stuart, D.I~~]]	+	[[Category: Malinauskas T]]
-	[[Category: ~~Ruza, R.R~~]]	+	[[Category: Owens R]]
-	[[Category: ~~Fry, E.E~~]]	+	[[Category: Ren J]]
-	[[Category: ~~Owens, R~~]]	+	[[Category: Ruza RR]]
-	[[Category: Zhou, D]]	+	[[Category: Shah PNM]]
		+	[[Category: Stuart DI]]
		+	[[Category: Zhao Y]]
		+	[[Category: Zhou D]]

OCA: Protected "6z97" [edit=sysop:move=sysop]

OCA — Wed, 10 Jun 2020 05:11:46 GMT

Protected "6z97" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:11, 10 June 2020

OCA: New page: '''Unreleased structure''' The entry 6z97 is ON HOLD Authors: Duyvesteyn, H.M.E., Ren, J., Zhao, Y., Zhou, D., Huo, J., Carrique, L., Malinauskas, T., Ruza, R.R., Shah, P.N.M., Fry, E.E...

OCA — Wed, 10 Jun 2020 05:11:45 GMT

New page: '''Unreleased structure''' The entry 6z97 is ON HOLD Authors: Duyvesteyn, H.M.E., Ren, J., Zhao, Y., Zhou, D., Huo, J., Carrique, L., Malinauskas, T., Ruza, R.R., Shah, P.N.M., Fry, E.E...

New page

'''Unreleased structure'''

The entry 6z97 is ON HOLD

Authors: Duyvesteyn, H.M.E., Ren, J., Zhao, Y., Zhou, D., Huo, J., Carrique, L., Malinauskas, T., Ruza, R.R., Shah, P.N.M., Fry, E.E., Owens, R., Stuart, D.I.

Description: Structure of the prefusion SARS-CoV-2 spike glycoprotein
[[Category: Unreleased Structures]]
[[Category: Carrique, L]]
[[Category: Ren, J]]
[[Category: Shah, P.N.M]]
[[Category: Malinauskas, T]]
[[Category: Duyvesteyn, H.M.E]]
[[Category: Huo, J]]
[[Category: Zhao, Y]]
[[Category: Stuart, D.I]]
[[Category: Ruza, R.R]]
[[Category: Fry, E.E]]
[[Category: Owens, R]]
[[Category: Zhou, D]]

6z97 - Revision history

OCA at 11:35, 23 September 2020

OCA at 14:44, 8 July 2020

OCA: Protected "6z97" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6z97 is ON HOLD Authors: Duyvesteyn, H.M.E., Ren, J., Zhao, Y., Zhou, D., Huo, J., Carrique, L., Malinauskas, T., Ruza, R.R., Shah, P.N.M., Fry, E.E...