OCA at 13:07, 1 February 2024

OCA — Thu, 01 Feb 2024 13:07:53 GMT

←Older revision		Revision as of 13:07, 1 February 2024
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-	====	+	==Crystal structure of the receptor binding domain of SARS-CoV-2 Spike glycoprotein in complex with FI-3A Fab==
-	<StructureSection load='7pqy' size='340' side='right'caption='[[7pqy]]' scene=''>	+	<StructureSection load='7pqy' size='340' side='right'caption='[[7pqy]], [[Resolution\|resolution]] 3.00Å' 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'>[[7pqy]] is a 6 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=7PQY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PQY 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=7pqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pqy OCA], [https://pdbe.org/7pqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pqy RCSB], [https://www.ebi.ac.uk/pdbsum/7pqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pqy 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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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=7pqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pqy OCA], [https://pdbe.org/7pqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pqy RCSB], [https://www.ebi.ac.uk/pdbsum/7pqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pqy 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 ==
		+	Background: Administration of potent anti-receptor-binding domain (RBD) monoclonal antibodies has been shown to curtail viral shedding and reduce hospitalization in patients with SARS-CoV-2 infection. However, the structure-function analysis of potent human anti-RBD monoclonal antibodies and its links to the formulation of antibody cocktails remains largely elusive. Methods: Previously, we isolated a panel of neutralizing anti-RBD monoclonal antibodies from convalescent patients and showed their neutralization efficacy in vitro. Here, we elucidate the mechanism of action of antibodies and dissect antibodies at the epitope level, which leads to a formation of a potent antibody cocktail. Results: We found that representative antibodies which target non-overlapping epitopes are effective against wild type virus and recently emerging variants of concern, whilst being encoded by antibody genes with few somatic mutations. Neutralization is associated with the inhibition of binding of viral RBD to ACE2 and possibly of the subsequent fusion process. Structural analysis of representative antibodies, by cryo-electron microscopy and crystallography, reveals that they have some unique aspects that are of potential value while sharing some features in common with previously reported neutralizing monoclonal antibodies. For instance, one has a common VH 3-53 public variable region yet is unusually resilient to mutation at residue 501 of the RBD. We evaluate the in vivo efficacy of an antibody cocktail consisting of two potent non-competing anti-RBD antibodies in a Syrian hamster model. We demonstrate that the cocktail prevents weight loss, reduces lung viral load and attenuates pulmonary inflammation in hamsters in both prophylactic and therapeutic settings. Although neutralization of one of these antibodies is abrogated by the mutations of variant B.1.351, it is also possible to produce a bi-valent cocktail of antibodies both of which are resilient to variants B.1.1.7, B.1.351 and B.1.617.2. Conclusions: These findings support the up-to-date and rational design of an anti-RBD antibody cocktail as a therapeutic candidate against COVID-19.
		+
		+	Structures and therapeutic potential of anti-RBD human monoclonal antibodies against SARS-CoV-2.,Huang KA, Zhou D, Tan TK, Chen C, Duyvesteyn HME, Zhao Y, Ginn HM, Qin L, Rijal P, Schimanski L, Donat R, Harding A, Gilbert-Jaramillo J, James W, Tree JA, Buttigieg K, Carroll M, Charlton S, Lien CE, Lin MY, Chen CP, Cheng SH, Chen X, Lin TY, Fry EE, Ren J, Ma C, Townsend AR, Stuart DI Theranostics. 2022 Jan 1;12(1):1-17. doi: 10.7150/thno.65563. eCollection 2022. PMID:34987630<ref>PMID:34987630</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7pqy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[Spike protein 3D structures\|Spike protein 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: Ren J]]
		+	[[Category: Stuart D]]
		+	[[Category: Zhou D]]

OCA at 07:01, 2 February 2022

OCA — Wed, 02 Feb 2022 07:01:50 GMT

←Older revision		Revision as of 07:01, 2 February 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7pqy ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7pqy' size='340' side='right'caption='[[7pqy]]' scene=''>
-	~~Authors~~: ~~Zhou, D~~.~~, Ren, J~~.~~, Stuart, D~~.	+	== 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 receptor binding domain of SARS-CoV~~-~~2 Spike glycoprotein in complex with FI-3A Fab~~	+	</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=7pqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pqy OCA], [https://pdbe.org/7pqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pqy RCSB], [https://www.ebi.ac.uk/pdbsum/7pqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pqy ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Ren, J~~]]	+	__TOC__
-	[[Category: ~~Stuart, D~~]]	+	</StructureSection>
-	[[Category: ~~Zhou, D~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 14:53, 20 October 2021

OCA — Wed, 20 Oct 2021 14:53:13 GMT

←Older revision		Revision as of 14:53, 20 October 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Zhou, D., Ren, J., Stuart, D.		Authors: Zhou, D., Ren, J., Stuart, D.
Line 7:		Line 7:
	Description: Crystal structure of the receptor binding domain of SARS-CoV-2 Spike glycoprotein in complex with FI-3A Fab		Description: Crystal structure of the receptor binding domain of SARS-CoV-2 Spike glycoprotein in complex with FI-3A Fab
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Ren, J]]
	[[Category: Stuart, D]]		[[Category: Stuart, D]]
	[[Category: Zhou, D]]		[[Category: Zhou, D]]
-	[[Category: Ren, J]]

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

OCA — Wed, 29 Sep 2021 07:38:55 GMT

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

←Older revision

Revision as of 07:38, 29 September 2021

OCA: New page: '''Unreleased structure''' The entry 7pqy is ON HOLD Authors: Zhou, D., Ren, J., Stuart, D. Description: Crystal structure of the receptor binding domain of SARS-CoV-2 Spike glycoprote...

OCA — Wed, 29 Sep 2021 07:38:55 GMT

New page: '''Unreleased structure''' The entry 7pqy is ON HOLD Authors: Zhou, D., Ren, J., Stuart, D. Description: Crystal structure of the receptor binding domain of SARS-CoV-2 Spike glycoprote...

New page

'''Unreleased structure'''

The entry 7pqy is ON HOLD

Authors: Zhou, D., Ren, J., Stuart, D.

Description: Crystal structure of the receptor binding domain of SARS-CoV-2 Spike glycoprotein in complex with FI-3A Fab
[[Category: Unreleased Structures]]
[[Category: Stuart, D]]
[[Category: Zhou, D]]
[[Category: Ren, J]]

7pqy - Revision history

OCA at 13:07, 1 February 2024

OCA at 07:01, 2 February 2022

OCA at 14:53, 20 October 2021

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

OCA: New page: '''Unreleased structure''' The entry 7pqy is ON HOLD Authors: Zhou, D., Ren, J., Stuart, D. Description: Crystal structure of the receptor binding domain of SARS-CoV-2 Spike glycoprote...