OCA at 14:54, 18 October 2023

OCA — Wed, 18 Oct 2023 14:54:35 GMT

←Older revision		Revision as of 14:54, 18 October 2023
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-	====	+	==Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody CV07-250==
-	<StructureSection load='6xkq' size='340' side='right'caption='[[6xkq]]' scene=''>	+	<StructureSection load='6xkq' size='340' side='right'caption='[[6xkq]], [[Resolution\|resolution]] 2.55Å' 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 [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xkq]] 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=6XKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XKQ 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=6xkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xkq OCA], [~~http~~://pdbe.org/6xkq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6xkq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6xkq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6xkq 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]] 2.55Å</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=6xkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xkq OCA], [https://pdbe.org/6xkq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xkq RCSB], [https://www.ebi.ac.uk/pdbsum/6xkq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xkq 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 emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC50 value of 3.1 ng/mL. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 A revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2-neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss, and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.
		+
		+	A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.,Kreye J, Reincke SM, Kornau HC, Sanchez-Sendin E, Corman VM, Liu H, Yuan M, Wu NC, Zhu X, Lee CD, Trimpert J, Holtje M, Dietert K, Stoffler L, von Wardenburg N, van Hoof S, Homeyer MA, Hoffmann J, Abdelgawad A, Gruber AD, Bertzbach LD, Vladimirova D, Li LY, Barthel PC, Skriner K, Hocke AC, Hippenstiel S, Witzenrath M, Suttorp N, Kurth F, Franke C, Endres M, Schmitz D, Jeworowski LM, Richter A, Schmidt ML, Schwarz T, Muller MA, Drosten C, Wendisch D, Sander LE, Osterrieder N, Wilson IA, Pruss H Cell. 2020 Nov 12;183(4):1058-1069.e19. doi: 10.1016/j.cell.2020.09.049. Epub, 2020 Sep 23. PMID:33058755<ref>PMID:33058755</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xkq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	== 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: Liu H]]
		+	[[Category: Wilson IA]]
		+	[[Category: Wu NC]]
		+	[[Category: Yuan M]]
		+	[[Category: Zhu X]]

OCA at 05:49, 14 October 2020

OCA — Wed, 14 Oct 2020 05:49:02 GMT

←Older revision		Revision as of 05:49, 14 October 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6xkq ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6xkq' size='340' side='right'caption='[[6xkq]]' scene=''>
-	~~Authors~~: ~~Yuan, M~~.~~, Liu, H~~.~~, Zhu, X~~.~~, Wu, N~~.C.~~, Wilson, I~~.A.	+	== 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 [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody CV07-250~~	+	</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=6xkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xkq OCA], [http://pdbe.org/6xkq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xkq RCSB], [http://www.ebi.ac.uk/pdbsum/6xkq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xkq ProSAT]</span></td></tr>
-	[~~[Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[~~[Category~~: ~~Wilson, I~~.A]]	+	__TOC__
-	[[~~Category~~: ~~Zhu~~, X]]	+	</StructureSection>
-	[~~[Category~~: Wu, N.C]]	+	[[Category: Large Structures]]
-	[[Category: ~~Liu, H~~]]	+	[[Category: Z-disk]]
-	[[Category: ~~Yuan, M~~]]	+

OCA at 08:08, 12 August 2020

OCA — Wed, 12 Aug 2020 08:08:28 GMT

←Older revision		Revision as of 08:08, 12 August 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6xkq is ON HOLD	+	The entry 6xkq is ON HOLD until Paper Publication

	Authors: Yuan, M., Liu, H., Zhu, X., Wu, N.C., Wilson, I.A.		Authors: Yuan, M., Liu, H., Zhu, X., Wu, N.C., Wilson, I.A.

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

OCA — Wed, 08 Jul 2020 10:55:00 GMT

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

←Older revision

Revision as of 10:55, 8 July 2020

OCA: New page: '''Unreleased structure''' The entry 6xkq is ON HOLD Authors: Yuan, M., Liu, H., Zhu, X., Wu, N.C., Wilson, I.A. Description: Crystal structure of SARS-CoV-2 receptor binding domain in...

OCA — Wed, 08 Jul 2020 10:54:59 GMT

New page: '''Unreleased structure''' The entry 6xkq is ON HOLD Authors: Yuan, M., Liu, H., Zhu, X., Wu, N.C., Wilson, I.A. Description: Crystal structure of SARS-CoV-2 receptor binding domain in...

New page

'''Unreleased structure'''

The entry 6xkq is ON HOLD

Authors: Yuan, M., Liu, H., Zhu, X., Wu, N.C., Wilson, I.A.

Description: Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody CV07-250
[[Category: Unreleased Structures]]
[[Category: Wilson, I.A]]
[[Category: Zhu, X]]
[[Category: Wu, N.C]]
[[Category: Liu, H]]
[[Category: Yuan, M]]

6xkq - Revision history

OCA at 14:54, 18 October 2023

OCA at 05:49, 14 October 2020

OCA at 08:08, 12 August 2020

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

OCA: New page: '''Unreleased structure''' The entry 6xkq is ON HOLD Authors: Yuan, M., Liu, H., Zhu, X., Wu, N.C., Wilson, I.A. Description: Crystal structure of SARS-CoV-2 receptor binding domain in...