OCA at 23:09, 27 December 2023

OCA — Wed, 27 Dec 2023 23:09:29 GMT

←Older revision		Revision as of 23:09, 27 December 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7y3n is ~~ON HOLD~~ ~~until 2024~~-12-11	+	==Crystal structure of SARS-CoV receptor binding domain in complex with human antibody BIOLS56==
		+	<StructureSection load='7y3n' size='340' side='right'caption='[[7y3n]], [[Resolution\|resolution]] 2.97Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7y3n]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y3N FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.97Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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=7y3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y3n OCA], [https://pdbe.org/7y3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y3n RCSB], [https://www.ebi.ac.uk/pdbsum/7y3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y3n ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SPIKE_SARS SPIKE_SARS] May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.<ref>PMID:31199522</ref> Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:14670965</ref> <ref>PMID:15496474</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]<ref>PMID:19321428</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Currently, monoclonal antibodies (MAbs) targeting the SARS-CoV-2 receptor binding domain (RBD) of spike (S) protein are classified into seven classes based on their binding epitopes. However, most of these antibodies are seriously impaired by SARS-CoV-2 Omicron and its subvariants, especially the recent BQ.1.1, XBB and its derivatives. Identification of broadly neutralizing MAbs against currently circulating variants is imperative. In this study, we identified a "breathing" cryptic epitope in the S protein, named as RBD-8. Two human MAbs, BIOLS56 and IMCAS74, were isolated recognizing this epitope with broad neutralization abilities against tested sarbecoviruses, including SARS-CoV, pangolin-origin coronaviruses, and all the SARS-CoV-2 variants tested (Omicron BA.4/BA.5, BQ.1.1, and XBB subvariants). Searching through the literature, some more RBD-8 MAbs were defined. More importantly, BIOLS56 rescues the immune-evaded antibody, RBD-5 MAb IMCAS-L4.65, by making a bispecific MAb, to neutralize BQ.1 and BQ.1.1, thereby producing an MAb to cover all the currently circulating Omicron subvariants. Structural analysis reveals that the neutralization effect of RBD-8 antibodies depends on the extent of epitope exposure, which is affected by the angle of antibody binding and the number of up-RBDs induced by angiotensin-converting enzyme 2 binding. This cryptic epitope which recognizes non- receptor binding motif (non-RBM) provides guidance for the development of universal therapeutic antibodies and vaccines against COVID-19.

-	~~Authors: Rao~~, X., ~~Chai~~, Y., Wu, Y., Gao, F.	+	Defining a de novo non-RBM antibody as RBD-8 and its synergistic rescue of immune-evaded antibodies to neutralize Omicron SARS-CoV-2.,Rao X, Zhao R, Tong Z, Guo S, Peng W, Liu K, Li S, Wu L, Tong J, Chai Y, Han P, Wang F, Jia P, Li Z, Zhao X, Li D, Zhang R, Zhang X, Zou W, Li W, Wang Q, Gao GF, Wu Y, Dai L, Gao F Proc Natl Acad Sci U S A. 2023 Dec 26;120(52):e2314193120. doi: , 10.1073/pnas.2314193120. Epub 2023 Dec 18. PMID:38109549<ref>PMID:38109549</ref>

-	~~Description: Crystal structure~~ of ~~SARS~~-~~CoV receptor binding domain in complex with human antibody BIOLS56~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Gao, F~~]]	+	<div class="pdbe-citations 7y3n" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Wu, Y~~]]	+	== References ==
-	[[Category: Chai, Y]]	+	<references/>
-	[[Category: Rao, X]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome-related coronavirus]]
		+	[[Category: Chai Y]]
		+	[[Category: Gao F]]
		+	[[Category: Rao X]]
		+	[[Category: Wu Y]]

OCA at 06:24, 16 August 2023

OCA — Wed, 16 Aug 2023 06:24:20 GMT

←Older revision		Revision as of 06:24, 16 August 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7y3n is ON HOLD until ~~Paper Publication~~	+	The entry 7y3n is ON HOLD until 2024-12-11

	Authors: Rao, X., Chai, Y., Wu, Y., Gao, F.		Authors: Rao, X., Chai, Y., Wu, Y., Gao, F.
Line 7:		Line 7:
	Description: Crystal structure of SARS-CoV receptor binding domain in complex with human antibody BIOLS56		Description: Crystal structure of SARS-CoV receptor binding domain in complex with human antibody BIOLS56
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Rao, X]]
	[[Category: Gao, F]]		[[Category: Gao, F]]
-	[[Category: Chai, Y]]
	[[Category: Wu, Y]]		[[Category: Wu, Y]]
		+	[[Category: Chai, Y]]
		+	[[Category: Rao, X]]

OCA: Protected "7y3n" [edit=sysop:move=sysop]

OCA — Wed, 22 Jun 2022 07:04:06 GMT

Protected "7y3n" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:04, 22 June 2022

OCA: New page: '''Unreleased structure''' The entry 7y3n is ON HOLD until Paper Publication Authors: Rao, X., Chai, Y., Wu, Y., Gao, F. Description: Crystal structure of SARS-CoV receptor binding dom...

OCA — Wed, 22 Jun 2022 07:04:05 GMT

New page: '''Unreleased structure''' The entry 7y3n is ON HOLD until Paper Publication Authors: Rao, X., Chai, Y., Wu, Y., Gao, F. Description: Crystal structure of SARS-CoV receptor binding dom...

New page

'''Unreleased structure'''

The entry 7y3n is ON HOLD until Paper Publication

Authors: Rao, X., Chai, Y., Wu, Y., Gao, F.

Description: Crystal structure of SARS-CoV receptor binding domain in complex with human antibody BIOLS56
[[Category: Unreleased Structures]]
[[Category: Rao, X]]
[[Category: Gao, F]]
[[Category: Chai, Y]]
[[Category: Wu, Y]]

7y3n - Revision history

OCA at 23:09, 27 December 2023

OCA at 06:24, 16 August 2023

OCA: Protected "7y3n" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7y3n is ON HOLD until Paper Publication Authors: Rao, X., Chai, Y., Wu, Y., Gao, F. Description: Crystal structure of SARS-CoV receptor binding dom...