OCA at 06:53, 9 August 2023

OCA — Wed, 09 Aug 2023 06:53:40 GMT

←Older revision		Revision as of 06:53, 9 August 2023
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-	====	+	==Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutralizing NTD-directed CV3-13 Fab isolated from convalescent individual==
-	<StructureSection load='7rq6' size='340' side='right'caption='[[7rq6]]' scene=''>	+	<StructureSection load='7rq6' size='340' side='right'caption='[[7rq6]], [[Resolution\|resolution]] 4.18Å' 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'>[[7rq6]] 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=7RQ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RQ6 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=7rq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rq6 OCA], [https://pdbe.org/7rq6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rq6 RCSB], [https://www.ebi.ac.uk/pdbsum/7rq6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rq6 ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 4.18Å</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=7rq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rq6 OCA], [https://pdbe.org/7rq6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rq6 RCSB], [https://www.ebi.ac.uk/pdbsum/7rq6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rq6 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 ==
		+	Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies.
		+
		+	A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection.,Beaudoin-Bussieres G, Chen Y, Ullah I, Prevost J, Tolbert WD, Symmes K, Ding S, Benlarbi M, Gong SY, Tauzin A, Gasser R, Chatterjee D, Vezina D, Goyette G, Richard J, Zhou F, Stamatatos L, McGuire AT, Charest H, Roger M, Pozharski E, Kumar P, Mothes W, Uchil PD, Pazgier M, Finzi A Cell Rep. 2022 Feb 15;38(7):110368. doi: 10.1016/j.celrep.2022.110368. Epub 2022 , Jan 25. PMID:35123652<ref>PMID:35123652</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7rq6" 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: Chen Y]]
		+	[[Category: Pazgier M]]
		+	[[Category: Pozharskiy E]]
		+	[[Category: Tolbert WD]]

OCA at 02:55, 21 April 2022

OCA — Thu, 21 Apr 2022 02:55:59 GMT

←Older revision		Revision as of 02:55, 21 April 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7rq6 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7rq6' size='340' side='right'caption='[[7rq6]]' scene=''>
-	~~Authors~~: ~~Chen, Y~~.~~, Pozharskiy, E~~.~~, Tolbert, W~~.D.~~, Pazgier, 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~~: ~~Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutralizing NTD-directed CV3-13 Fab isolated from convalescent individual~~	+	</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=7rq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rq6 OCA], [https://pdbe.org/7rq6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rq6 RCSB], [https://www.ebi.ac.uk/pdbsum/7rq6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rq6 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[~~[Category~~: ~~Pozharskiy~~, E]]	+	__TOC__
-	[~~[Category~~: ~~Pazgier~~, M]]	+	</StructureSection>
-	[[Category: ~~Tolbert, W.D~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Chen, Y~~]]	+	[[Category: Z-disk]]

OCA at 08:14, 15 September 2021

OCA — Wed, 15 Sep 2021 08:14:38 GMT

←Older revision		Revision as of 08:14, 15 September 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7rq6 is ON HOLD	+	The entry 7rq6 is ON HOLD until Paper Publication

	Authors: Chen, Y., Pozharskiy, E., Tolbert, W.D., Pazgier, M.		Authors: Chen, Y., Pozharskiy, E., Tolbert, W.D., Pazgier, M.

OCA: Protected "7rq6" [edit=sysop:move=sysop]

OCA — Wed, 11 Aug 2021 05:13:47 GMT

Protected "7rq6" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:13, 11 August 2021

OCA: New page: '''Unreleased structure''' The entry 7rq6 is ON HOLD Authors: Chen, Y., Pozharskiy, E., Tolbert, W.D., Pazgier, M. Description: Cryo-EM structure of SARS-CoV-2 spike in complex with no...

OCA — Wed, 11 Aug 2021 05:13:46 GMT

New page: '''Unreleased structure''' The entry 7rq6 is ON HOLD Authors: Chen, Y., Pozharskiy, E., Tolbert, W.D., Pazgier, M. Description: Cryo-EM structure of SARS-CoV-2 spike in complex with no...

New page

'''Unreleased structure'''

The entry 7rq6 is ON HOLD

Authors: Chen, Y., Pozharskiy, E., Tolbert, W.D., Pazgier, M.

Description: Cryo-EM structure of SARS-CoV-2 spike in complex with non-neutralizing NTD-directed CV3-13 Fab isolated from convalescent individual
[[Category: Unreleased Structures]]
[[Category: Pozharskiy, E]]
[[Category: Pazgier, M]]
[[Category: Tolbert, W.D]]
[[Category: Chen, Y]]

7rq6 - Revision history

OCA at 06:53, 9 August 2023

OCA at 02:55, 21 April 2022

OCA at 08:14, 15 September 2021

OCA: Protected "7rq6" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7rq6 is ON HOLD Authors: Chen, Y., Pozharskiy, E., Tolbert, W.D., Pazgier, M. Description: Cryo-EM structure of SARS-CoV-2 spike in complex with no...