OCA at 16:27, 18 October 2023

2023-10-18T16:27:55Z

← Older revision		Revision as of 16:27, 18 October 2023
Line 1:		Line 1:

	====		==Crystal structure of CV3-25 Fab bound to SARS-CoV-2 spike stem helix peptide==
	<StructureSection load='7raq' size='340' side='right'caption='[[7raq]]' scene=''>		<StructureSection load='7raq' size='340' side='right'caption='[[7raq]], [[Resolution\|resolution]] 1.74Å' 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'>[[7raq]] 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=7RAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RAQ 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=7raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7raq OCA], [https://pdbe.org/7raq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7raq RCSB], [https://www.ebi.ac.uk/pdbsum/7raq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7raq 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]] 1.74Å</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=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7raq OCA], [https://pdbe.org/7raq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7raq RCSB], [https://www.ebi.ac.uk/pdbsum/7raq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7raq 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 ==
			Three betacoronaviruses have crossed the species barrier and established human-to-human transmission causing significant morbidity and mortality in the past 20 years. The most current and widespread of these is SARS-CoV-2. The identification of CoVs with zoonotic potential in animal reservoirs suggests that additional outbreaks could occur. Monoclonal antibodies targeting conserved neutralizing epitopes on diverse CoVs can form the basis for prophylaxis and therapeutic treatments and enable the design of vaccines aimed at providing pan-CoV protection. We previously identified a neutralizing monoclonal antibody, CV3-25 that binds to the SARS-CoV-2 spike, neutralizes the SARS-CoV-2 Beta variant comparably to the ancestral Wuhan Hu-1 strain, cross neutralizes SARS-CoV-1 and binds to recombinant proteins derived from the spike-ectodomains of HCoV-OC43 and HCoV-HKU1. Here, we show that the neutralizing activity of CV3-25 is maintained against the Alpha, Delta, Gamma and Omicron variants of concern as well as a SARS-CoV-like bat coronavirus with zoonotic potential by binding to a conserved linear peptide in the stem-helix region. Negative stain electron microscopy and a 1.74 A crystal structure of a CV3-25/peptide complex demonstrates that CV3-25 binds to the base of the stem helix at the HR2 boundary to an epitope that is distinct from other stem-helix directed neutralizing mAbs.

			Structural definition of a pan-sarbecovirus neutralizing epitope on the spike S2 subunit.,Hurlburt NK, Homad LJ, Sinha I, Jennewein MF, MacCamy AJ, Wan YH, Boonyaratanakornkit J, Sholukh AM, Jackson AM, Zhou P, Burton DR, Andrabi R, Ozorowski G, Ward AB, Stamatatos L, Pancera M, McGuire AT Commun Biol. 2022 Apr 11;5(1):342. doi: 10.1038/s42003-022-03262-7. PMID:35411021<ref>PMID:35411021</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7raq" 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: Hurlburt NK]]
			[[Category: Pancera M]]

OCA at 09:47, 13 April 2022

2022-04-13T09:47:46Z

← Older revision		Revision as of 09:47, 13 April 2022
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 7raq ~~is ON HOLD until Paper Publication~~		====
			<StructureSection load='7raq' size='340' side='right'caption='[[7raq]]' scene=''>
	~~Authors~~: ~~Hurlburt, N~~.K.~~, Pancera, M~~.		== 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 CV3~~-~~25 Fab bound to SARS-CoV-2 spike stem helix peptide~~		</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=7raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7raq OCA], [https://pdbe.org/7raq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7raq RCSB], [https://www.ebi.ac.uk/pdbsum/7raq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7raq ProSAT]</span></td></tr>
	[[~~Category~~: ~~Unreleased Structures~~]]		</table>
	[[Category: ~~Hurlburt, N.K~~]]		__TOC__
	[[Category: ~~Pancera, M~~]]		</StructureSection>
			[[Category: Large Structures]]
			[[Category: Z-disk]]

OCA at 05:08, 11 August 2021

2021-08-11T05:08:25Z

← Older revision		Revision as of 05:08, 11 August 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7raq is ON HOLD		The entry 7raq is ON HOLD until Paper Publication

	Authors: Hurlburt, N.K., Pancera, M.		Authors: Hurlburt, N.K., Pancera, M.

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

2021-07-14T08:54:52Z

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

← Older revision	Revision as of 08:54, 14 July 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7raq is ON HOLD Authors: Hurlburt, N.K., Pancera, M. Description: Crystal structure of CV3-25 Fab bound to SARS-CoV-2 spike stem helix peptide [[Ca...

2021-07-14T08:54:51Z

New page: '''Unreleased structure''' The entry 7raq is ON HOLD Authors: Hurlburt, N.K., Pancera, M. Description: Crystal structure of CV3-25 Fab bound to SARS-CoV-2 spike stem helix peptide [[Ca...

New page

'''Unreleased structure'''

The entry 7raq is ON HOLD

Authors: Hurlburt, N.K., Pancera, M.

Description: Crystal structure of CV3-25 Fab bound to SARS-CoV-2 spike stem helix peptide
[[Category: Unreleased Structures]]
[[Category: Hurlburt, N.K]]
[[Category: Pancera, M]]

7raq - Revision history

OCA at 16:27, 18 October 2023

OCA at 09:47, 13 April 2022

OCA at 05:08, 11 August 2021

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

OCA: New page: '''Unreleased structure''' The entry 7raq is ON HOLD Authors: Hurlburt, N.K., Pancera, M. Description: Crystal structure of CV3-25 Fab bound to SARS-CoV-2 spike stem helix peptide [[Ca...