OCA at 21:13, 28 June 2023

OCA — Wed, 28 Jun 2023 21:13:51 GMT

←Older revision		Revision as of 21:13, 28 June 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 7ytn is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of SARS-CoV-2 Alpha RBD in complex with the D27LEY neutralizing antibody Fab fragment==
		+	<StructureSection load='7ytn' size='340' side='right'caption='[[7ytn]], [[Resolution\|resolution]] 3.51Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7ytn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [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=7YTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YTN 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]] 3.51Å</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=7ytn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ytn OCA], [https://pdbe.org/7ytn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ytn RCSB], [https://www.ebi.ac.uk/pdbsum/7ytn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ytn 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 ==
		+	More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses.

-	~~Authors: Jeong, B.S~~., Jeon, ~~J.Y.~~, Oh, B.H.	+	Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses.,Jeong BS, Jeon JY, Lai CJ, Yun HY, Jung JU, Oh BH Front Immunol. 2022 Nov 17;13:1049867. doi: 10.3389/fimmu.2022.1049867. , eCollection 2022. PMID:36466915<ref>PMID:36466915</ref>

-	~~Description: Crystal structure~~ of ~~SARS~~-~~CoV~~-~~2 Alpha RBD in complex with the D27LEY neutralizing antibody Fab fragment~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Jeong, B.S~~]]	+	<div class="pdbe-citations 7ytn" style="background-color:#fffaf0;"></div>
-	[[Category: Jeon~~, J.Y~~]]	+	== References ==
-	[[Category: Oh~~, B.H~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Jeon JY]]
		+	[[Category: Jeong BS]]
		+	[[Category: Oh BH]]

OCA at 04:28, 28 September 2022

OCA — Wed, 28 Sep 2022 04:28:21 GMT

←Older revision		Revision as of 04:28, 28 September 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7ytn is ON HOLD	+	The entry 7ytn is ON HOLD until Paper Publication

	Authors: Jeong, B.S., Jeon, J.Y., Oh, B.H.		Authors: Jeong, B.S., Jeon, J.Y., Oh, B.H.

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

OCA — Thu, 25 Aug 2022 03:37:30 GMT

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

←Older revision

Revision as of 03:37, 25 August 2022

OCA: New page: '''Unreleased structure''' The entry 7ytn is ON HOLD Authors: Jeong, B.S., Jeon, J.Y., Oh, B.H. Description: Crystal structure of SARS-CoV-2 Alpha RBD in complex with the D27LEY neutra...

OCA — Thu, 25 Aug 2022 03:37:29 GMT

New page: '''Unreleased structure''' The entry 7ytn is ON HOLD Authors: Jeong, B.S., Jeon, J.Y., Oh, B.H. Description: Crystal structure of SARS-CoV-2 Alpha RBD in complex with the D27LEY neutra...

New page

'''Unreleased structure'''

The entry 7ytn is ON HOLD

Authors: Jeong, B.S., Jeon, J.Y., Oh, B.H.

Description: Crystal structure of SARS-CoV-2 Alpha RBD in complex with the D27LEY neutralizing antibody Fab fragment
[[Category: Unreleased Structures]]
[[Category: Jeong, B.S]]
[[Category: Jeon, J.Y]]
[[Category: Oh, B.H]]

7ytn - Revision history

OCA at 21:13, 28 June 2023

OCA at 04:28, 28 September 2022

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

OCA: New page: '''Unreleased structure''' The entry 7ytn is ON HOLD Authors: Jeong, B.S., Jeon, J.Y., Oh, B.H. Description: Crystal structure of SARS-CoV-2 Alpha RBD in complex with the D27LEY neutra...