OCA at 17:28, 29 November 2023

OCA — Wed, 29 Nov 2023 17:28:45 GMT

←Older revision		Revision as of 17:28, 29 November 2023
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-	====	+	==Crystal structure of the SARS-CoV-2 RBD in complex with a human single domain antibody n3113==
-	<StructureSection load='7vnb' size='340' side='right'caption='[[7vnb]]' scene=''>	+	<StructureSection load='7vnb' size='340' side='right'caption='[[7vnb]], [[Resolution\|resolution]] 2.27Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7vnb]] is a 2 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=7VNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VNB FirstGlance]. <br>
-	</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=7vnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vnb OCA], [https://pdbe.org/7vnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vnb RCSB], [https://www.ebi.ac.uk/pdbsum/7vnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vnb ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.27Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7vnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vnb OCA], [https://pdbe.org/7vnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vnb RCSB], [https://www.ebi.ac.uk/pdbsum/7vnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vnb 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 current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.
		+
		+	A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants.,Yang Z, Wang Y, Jin Y, Zhu Y, Wu Y, Li C, Kong Y, Song W, Tian X, Zhan W, Huang A, Zhou S, Xia S, Tian X, Peng C, Chen C, Shi Y, Hu G, Du S, Wang Y, Xie Y, Jiang S, Lu L, Sun L, Song Y, Ying T Signal Transduct Target Ther. 2021 Nov 3;6(1):378. doi: , 10.1038/s41392-021-00810-1. PMID:34732694<ref>PMID:34732694</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7vnb" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z~~-disk~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Jin Y]]
		+	[[Category: Kong Y]]
		+	[[Category: Wang Y]]
		+	[[Category: Wu Y]]
		+	[[Category: Yang Z]]
		+	[[Category: Ying T]]

OCA at 12:39, 24 November 2021

OCA — Wed, 24 Nov 2021 12:39:39 GMT

←Older revision		Revision as of 12:39, 24 November 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7vnb ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7vnb' size='340' side='right'caption='[[7vnb]]' scene=''>
-	~~Authors~~: ~~Yang, Z~~.~~, Wang, Y~~.~~, Kong, Y~~.~~, Jin, Y~~.~~, Wu, Y~~.~~, Ying, T~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of the SARS-CoV-2 RBD in complex with a human single domain antibody n3113~~	+	</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=7vnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vnb OCA], [https://pdbe.org/7vnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vnb RCSB], [https://www.ebi.ac.uk/pdbsum/7vnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vnb ProSAT]</span></td></tr>
-	[~~[Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[~~[Category~~: ~~Yang~~, ~~Z]]~~	+	__TOC__
-	[~~[Category~~: ~~Wang, Y]~~]	+	</StructureSection>
-	[[~~Category~~: ~~Kong, Y~~]]	+	[[Category: Large Structures]]
-	[~~[Category~~: Wu, Y]]	+	[[Category: Z-disk]]
-	[[Category: ~~Ying, T~~]]	+
-	[[Category: ~~Jin, Y~~]]	+

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

OCA — Wed, 20 Oct 2021 15:16:10 GMT

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

←Older revision

Revision as of 15:16, 20 October 2021

OCA: New page: '''Unreleased structure''' The entry 7vnb is ON HOLD until Paper Publication Authors: Yang, Z., Wang, Y., Kong, Y., Jin, Y., Wu, Y., Ying, T. Description: Crystal structure of the SARS...

OCA — Wed, 20 Oct 2021 15:16:08 GMT

New page: '''Unreleased structure''' The entry 7vnb is ON HOLD until Paper Publication Authors: Yang, Z., Wang, Y., Kong, Y., Jin, Y., Wu, Y., Ying, T. Description: Crystal structure of the SARS...

New page

'''Unreleased structure'''

The entry 7vnb is ON HOLD until Paper Publication

Authors: Yang, Z., Wang, Y., Kong, Y., Jin, Y., Wu, Y., Ying, T.

Description: Crystal structure of the SARS-CoV-2 RBD in complex with a human single domain antibody n3113
[[Category: Unreleased Structures]]
[[Category: Yang, Z]]
[[Category: Wang, Y]]
[[Category: Kong, Y]]
[[Category: Wu, Y]]
[[Category: Ying, T]]
[[Category: Jin, Y]]

7vnb - Revision history

OCA at 17:28, 29 November 2023

OCA at 12:39, 24 November 2021

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

OCA: New page: '''Unreleased structure''' The entry 7vnb is ON HOLD until Paper Publication Authors: Yang, Z., Wang, Y., Kong, Y., Jin, Y., Wu, Y., Ying, T. Description: Crystal structure of the SARS...