OCA at 16:06, 18 October 2023

2023-10-18T16:06:09Z

←Older revision		Revision as of 16:06, 18 October 2023
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-	====	+	==Structure of the SARS-CoV-2 RBD in complex with neutralizing antibodies BG4-25 and CR3022==
-	<StructureSection load='7m6d' size='340' side='right'caption='[[7m6d]]' scene=''>	+	<StructureSection load='7m6d' size='340' side='right'caption='[[7m6d]], [[Resolution\|resolution]] 3.10Å' 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'>[[7m6d]] is a 5 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=7M6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M6D 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=7m6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m6d OCA], [https://pdbe.org/7m6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m6d RCSB], [https://www.ebi.ac.uk/pdbsum/7m6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m6d 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]] 3.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=7m6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m6d OCA], [https://pdbe.org/7m6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m6d RCSB], [https://www.ebi.ac.uk/pdbsum/7m6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m6d 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 ==
		+	Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.
		+
		+	B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV.,Scheid JF, Barnes CO, Eraslan B, Hudak A, Keeffe JR, Cosimi LA, Brown EM, Muecksch F, Weisblum Y, Zhang S, Delorey T, Woolley AE, Ghantous F, Park SM, Phillips D, Tusi B, Huey-Tubman KE, Cohen AA, Gnanapragasam PNP, Rzasa K, Hatziioanno T, Durney MA, Gu X, Tada T, Landau NR, West AP Jr, Rozenblatt-Rosen O, Seaman MS, Baden LR, Graham DB, Deguine J, Bieniasz PD, Regev A, Hung D, Bjorkman PJ, Xavier RJ Cell. 2021 Jun 10;184(12):3205-3221.e24. doi: 10.1016/j.cell.2021.04.032. Epub , 2021 Apr 24. PMID:34015271<ref>PMID:34015271</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7m6d" 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: Barnes CO]]
		+	[[Category: Bjorkman PJ]]

OCA at 08:54, 5 May 2021

2021-05-05T08:54:28Z

←Older revision		Revision as of 08:54, 5 May 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7m6d ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7m6d' size='340' side='right'caption='[[7m6d]]' scene=''>
-	~~Authors~~: ~~Barnes, C~~.O.~~, Bjorkman, P~~.J.	+	== 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~~: ~~Structure of the SARS~~-~~CoV-2 RBD in complex with neutralizing antibodies BG4-25 and CR3022~~	+	</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=7m6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m6d OCA], [https://pdbe.org/7m6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m6d RCSB], [https://www.ebi.ac.uk/pdbsum/7m6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m6d ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Barnes, C.O~~]]	+	__TOC__
-	[[Category: ~~Bjorkman, P.J~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA: Protected "7m6d" [edit=sysop:move=sysop]

2021-03-31T09:26:02Z

Protected "7m6d" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:26, 31 March 2021

OCA: New page: '''Unreleased structure''' The entry 7m6d is ON HOLD Authors: Barnes, C.O., Bjorkman, P.J. Description: Structure of the SARS-CoV-2 RBD in complex with neutralizing antibodies BG4-25 a...

2021-03-31T09:26:00Z

New page: '''Unreleased structure''' The entry 7m6d is ON HOLD Authors: Barnes, C.O., Bjorkman, P.J. Description: Structure of the SARS-CoV-2 RBD in complex with neutralizing antibodies BG4-25 a...

New page

'''Unreleased structure'''

The entry 7m6d is ON HOLD

Authors: Barnes, C.O., Bjorkman, P.J.

Description: Structure of the SARS-CoV-2 RBD in complex with neutralizing antibodies BG4-25 and CR3022
[[Category: Unreleased Structures]]
[[Category: Barnes, C.O]]
[[Category: Bjorkman, P.J]]

7m6d - Revision history

OCA at 16:06, 18 October 2023

OCA at 08:54, 5 May 2021

OCA: Protected "7m6d" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7m6d is ON HOLD Authors: Barnes, C.O., Bjorkman, P.J. Description: Structure of the SARS-CoV-2 RBD in complex with neutralizing antibodies BG4-25 a...