OCA at 15:39, 18 October 2023

OCA — Wed, 18 Oct 2023 15:39:53 GMT

←Older revision		Revision as of 15:39, 18 October 2023
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-	====	+	==Crystal structure of SARS-CoV-2 spike RBD in complex with human monoclonal antibody AZD8895==
-	<StructureSection load='7l7d' size='340' side='right'caption='[[7l7d]]' scene=''>	+	<StructureSection load='7l7d' size='340' side='right'caption='[[7l7d]], [[Resolution\|resolution]] 2.50Å' 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'>[[7l7d]] 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=7L7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L7D 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=7l7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7d OCA], [https://pdbe.org/7l7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7d RCSB], [https://www.ebi.ac.uk/pdbsum/7l7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7d 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]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7l7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7d OCA], [https://pdbe.org/7l7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7d RCSB], [https://www.ebi.ac.uk/pdbsum/7l7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7d 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 ==
		+	Understanding the molecular basis for immune recognition of SARS-CoV-2 spike glycoprotein antigenic sites will inform the development of improved therapeutics. We determined the structures of two human monoclonal antibodies-AZD8895 and AZD1061-which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor-binding domain (RBD) of SARS-CoV-2 to define the genetic and structural basis of neutralization. AZD8895 forms an 'aromatic cage' at the heavy/light chain interface using germ line-encoded residues in complementarity-determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals. AZD1061 has an unusually long LCDR1; the HCDR3 makes interactions with the opposite face of the RBD from that of AZD8895. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the crucial binding residues of both antibodies and identified positions of concern with regards to virus escape from antibody-mediated neutralization. Both AZD8895 and AZD1061 have strong neutralizing activity against SARS-CoV-2 and variants of concern with antigenic substitutions in the RBD. We conclude that germ line-encoded antibody features enable recognition of the SARS-CoV-2 spike RBD and demonstrate the utility of the cocktail AZD7442 in neutralizing emerging variant viruses.
		+
		+	Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail.,Dong J, Zost SJ, Greaney AJ, Starr TN, Dingens AS, Chen EC, Chen RE, Case JB, Sutton RE, Gilchuk P, Rodriguez J, Armstrong E, Gainza C, Nargi RS, Binshtein E, Xie X, Zhang X, Shi PY, Logue J, Weston S, McGrath ME, Frieman MB, Brady T, Tuffy KM, Bright H, Loo YM, McTamney PM, Esser MT, Carnahan RH, Diamond MS, Bloom JD, Crowe JE Jr Nat Microbiol. 2021 Oct;6(10):1233-1244. doi: 10.1038/s41564-021-00972-2. Epub , 2021 Sep 21. PMID:34548634<ref>PMID:34548634</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7l7d" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 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: Crowe JE]]
		+	[[Category: Dong J]]

OCA at 07:17, 16 March 2022

OCA — Wed, 16 Mar 2022 07:17:15 GMT

←Older revision		Revision as of 07:17, 16 March 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7l7d ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7l7d' size='340' side='right'caption='[[7l7d]]' scene=''>
-	~~Authors~~: ~~Dong, J~~.~~, Crowe, J~~.E.	+	== 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 SARS~~-~~CoV-2 spike RBD in complex with human monoclonal antibody AZD8895~~	+	</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=7l7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l7d OCA], [https://pdbe.org/7l7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l7d RCSB], [https://www.ebi.ac.uk/pdbsum/7l7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l7d ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Crowe, J.E~~]]	+	__TOC__
-	[[Category: ~~Dong, J~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:06, 25 August 2021

OCA — Wed, 25 Aug 2021 05:06:58 GMT

←Older revision		Revision as of 05:06, 25 August 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7l7d is ON HOLD ~~until Paper Publication~~	+	The entry 7l7d is ON HOLD

-	Authors: Dong, J.	+	Authors: Dong, J., Crowe, J.E.

-	Description: Crystal structure of SARS-CoV-2 spike RBD in complex with human monoclonal antibody ~~COV2-2196~~	+	Description: Crystal structure of SARS-CoV-2 spike RBD in complex with human monoclonal antibody AZD8895
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Crowe, J.E]]
	[[Category: Dong, J]]		[[Category: Dong, J]]

OCA: Protected "7l7d" [edit=sysop:move=sysop]

OCA — Wed, 06 Jan 2021 05:52:04 GMT

Protected "7l7d" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:52, 6 January 2021

OCA: New page: '''Unreleased structure''' The entry 7l7d is ON HOLD until Paper Publication Authors: Dong, J. Description: Crystal structure of SARS-CoV-2 spike RBD in complex with human monoclonal a...

OCA — Wed, 06 Jan 2021 05:52:01 GMT

New page: '''Unreleased structure''' The entry 7l7d is ON HOLD until Paper Publication Authors: Dong, J. Description: Crystal structure of SARS-CoV-2 spike RBD in complex with human monoclonal a...

New page

'''Unreleased structure'''

The entry 7l7d is ON HOLD until Paper Publication

Authors: Dong, J.

Description: Crystal structure of SARS-CoV-2 spike RBD in complex with human monoclonal antibody COV2-2196
[[Category: Unreleased Structures]]
[[Category: Dong, J]]

7l7d - Revision history

OCA at 15:39, 18 October 2023

OCA at 07:17, 16 March 2022

OCA at 05:06, 25 August 2021

OCA: Protected "7l7d" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7l7d is ON HOLD until Paper Publication Authors: Dong, J. Description: Crystal structure of SARS-CoV-2 spike RBD in complex with human monoclonal a...