OCA at 16:51, 18 October 2023

2023-10-18T16:51:51Z

←Older revision		Revision as of 16:51, 18 October 2023
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-	====	+	==Crystal structure of neutralizing antibody 10-28 in complex with SARS-CoV-2 spike receptor binding domain (RBD)==
-	<StructureSection load='7si2' size='340' side='right'caption='[[7si2]]' scene=''>	+	<StructureSection load='7si2' size='340' side='right'caption='[[7si2]], [[Resolution\|resolution]] 3.20Å' 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'>[[7si2]] 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_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SI2 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=7si2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7si2 OCA], [https://pdbe.org/7si2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7si2 RCSB], [https://www.ebi.ac.uk/pdbsum/7si2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7si2 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]] 3.2Å</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=7si2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7si2 OCA], [https://pdbe.org/7si2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7si2 RCSB], [https://www.ebi.ac.uk/pdbsum/7si2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7si2 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 devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.
		+
		+	An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses.,Liu L, Iketani S, Guo Y, Reddem ER, Casner RG, Nair MS, Yu J, Chan JF, Wang M, Cerutti G, Li Z, Morano NC, Castagna CD, Corredor L, Chu H, Yuan S, Poon VK, Chan CC, Chen Z, Luo Y, Cunningham M, Chavez A, Yin MT, Perlin DS, Tsuji M, Yuen KY, Kwong PD, Sheng Z, Huang Y, Shapiro L, Ho DD Sci Transl Med. 2022 May 25;14(646):eabn6859. doi: 10.1126/scitranslmed.abn6859. , Epub 2022 May 25. PMID:35438546<ref>PMID:35438546</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7si2" 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: Reddem ER]]
		+	[[Category: Shapiro L]]

OCA at 11:39, 27 April 2022

2022-04-27T11:39:31Z

←Older revision		Revision as of 11:39, 27 April 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7si2 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7si2' size='340' side='right'caption='[[7si2]]' scene=''>
-	~~Authors~~: ~~Reddem, E~~.R.~~, Shapiro, L~~.	+	== 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 neutralizing antibody 10~~-~~28 in complex with SARS-CoV-2 spike receptor binding domain (RBD)~~	+	</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=7si2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7si2 OCA], [https://pdbe.org/7si2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7si2 RCSB], [https://www.ebi.ac.uk/pdbsum/7si2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7si2 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Shapiro, L~~]]	+	__TOC__
-	[[Category: ~~Reddem, E.R~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 08:31, 8 December 2021

2021-12-08T08:31:55Z

←Older revision		Revision as of 08:31, 8 December 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7si2 is ON HOLD	+	The entry 7si2 is ON HOLD until Paper Publication

	Authors: Reddem, E.R., Shapiro, L.		Authors: Reddem, E.R., Shapiro, L.

OCA: Protected "7si2" [edit=sysop:move=sysop]

2021-10-20T15:09:06Z

Protected "7si2" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:09, 20 October 2021

OCA: New page: '''Unreleased structure''' The entry 7si2 is ON HOLD Authors: Reddem, E.R., Shapiro, L. Description: Crystal structure of neutralizing antibody 10-28 in complex with SARS-CoV-2 spike r...

2021-10-20T15:09:05Z

New page: '''Unreleased structure''' The entry 7si2 is ON HOLD Authors: Reddem, E.R., Shapiro, L. Description: Crystal structure of neutralizing antibody 10-28 in complex with SARS-CoV-2 spike r...

New page

'''Unreleased structure'''

The entry 7si2 is ON HOLD

Authors: Reddem, E.R., Shapiro, L.

Description: Crystal structure of neutralizing antibody 10-28 in complex with SARS-CoV-2 spike receptor binding domain (RBD)
[[Category: Unreleased Structures]]
[[Category: Shapiro, L]]
[[Category: Reddem, E.R]]

7si2 - Revision history

OCA at 16:51, 18 October 2023

OCA at 11:39, 27 April 2022

OCA at 08:31, 8 December 2021

OCA: Protected "7si2" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7si2 is ON HOLD Authors: Reddem, E.R., Shapiro, L. Description: Crystal structure of neutralizing antibody 10-28 in complex with SARS-CoV-2 spike r...