OCA at 14:12, 29 November 2023

2023-11-29T14:12:22Z

←Older revision		Revision as of 14:12, 29 November 2023
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-	'''Unreleased structure'''

-	The entry ~~8uuo~~ is ~~ON HOLD~~	+	==Prototypic SARS-CoV-2 spike (containing V417) in the open conformation==
		+	<StructureSection load='8uuo' size='340' side='right'caption='[[8uuo]], [[Resolution\|resolution]] 3.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8uuo]] 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=8UUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UUO FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.9Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=8uuo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uuo OCA], [https://pdbe.org/8uuo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uuo RCSB], [https://www.ebi.ac.uk/pdbsum/8uuo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uuo ProSAT]</span></td></tr>
		+	</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 spike protein plays a key role in mediating viral entry and inducing host immune responses. It can adopt either an open or closed conformation based on the position of its receptor-binding domain (RBD). It is yet unclear what cause these conformational changes or how they influence the spike's functions. Here we show that Lys417 in the RBD plays dual roles in the spike's structure: it stabilizes the closed conformation of the trimeric spike by mediating inter-spike-subunit interactions; it also directly interacts with ACE2 receptor. Hence, a K417V mutation has opposing effects on the spike's function: it opens up the spike for better ACE2 binding while weakening the RBD's direct binding to ACE2. The net outcomes of this mutation are to allow the spike to bind ACE2 with higher probability, mediate viral entry more efficiently, but become more exposed to neutralizing antibodies. Given that residue 417 has been a viral mutational hotspot, SARS-CoV-2 may have been evolving to strike a balance between infection potency and immune evasion, contributing to its pandemic spread.

-	~~Authors~~:	+	Lys417 acts as a molecular switch that regulates the conformation of SARS-CoV-2 spike protein.,Geng Q, Wan Y, Hsueh FC, Shang J, Ye G, Bu F, Herbst M, Wilkens R, Liu B, Li F Elife. 2023 Nov 22;12:e74060. doi: 10.7554/eLife.74060. PMID:37991488<ref>PMID:37991488</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8uuo" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Geng Q]]
		+	[[Category: Li F]]
		+	[[Category: Liu B]]

OCA: Protected "8uuo" [edit=sysop:move=sysop]

2023-11-08T09:20:28Z

Protected "8uuo" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:20, 8 November 2023

OCA: New page: '''Unreleased structure''' The entry 8uuo is ON HOLD Authors: Description: Category: Unreleased Structures

2023-11-08T09:20:27Z

New page: '''Unreleased structure''' The entry 8uuo is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8uuo is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8uuo - Revision history

OCA at 14:12, 29 November 2023

OCA: Protected "8uuo" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8uuo is ON HOLD Authors: Description: Category: Unreleased Structures