7wbz - Revision history

OCA at 17:38, 29 November 2023

OCA — Wed, 29 Nov 2023 17:38:57 GMT

←Older revision		Revision as of 17:38, 29 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7wbz]] 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=7WBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WBZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[7wbz]] 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=7WBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WBZ FirstGlance]. <br>
-	</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>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.42Å</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=7wbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wbz OCA], [https://pdbe.org/7wbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wbz RCSB], [https://www.ebi.ac.uk/pdbsum/7wbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wbz ProSAT]</span></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=7wbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wbz OCA], [https://pdbe.org/7wbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wbz RCSB], [https://www.ebi.ac.uk/pdbsum/7wbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wbz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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]	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7wbz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7wbz" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:31, 7 September 2022

OCA — Wed, 07 Sep 2022 19:31:16 GMT

←Older revision		Revision as of 19:31, 7 September 2022
Line 1:		Line 1:

-	====	+	==Crystal structure of the SARS-Cov-2 RBD in complex with Fab 2303==
-	<StructureSection load='7wbz' size='340' side='right'caption='[[7wbz]]' scene=''>	+	<StructureSection load='7wbz' size='340' side='right'caption='[[7wbz]], [[Resolution\|resolution]] 2.42Å' 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'>[[7wbz]] 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=7WBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WBZ 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=7wbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wbz OCA], [https://pdbe.org/7wbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wbz RCSB], [https://www.ebi.ac.uk/pdbsum/7wbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wbz ProSAT]</span></td></tr>	+	</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=7wbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wbz OCA], [https://pdbe.org/7wbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wbz RCSB], [https://www.ebi.ac.uk/pdbsum/7wbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wbz 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 ==
		+	As new variants of SARS-CoV-2 continue to emerge, it is important to assess the cross-neutralizing capabilities of antibodies naturally elicited during wild type SARS-CoV-2 infection. In the present study, we evaluate the activity of nine anti-SARS-CoV-2 monoclonal antibodies (mAbs), previously isolated from convalescent donors infected with the Wuhan-Hu-1 strain, against the SARS-CoV-2 variants of concern (VOC) Alpha, Beta, Gamma, Delta and Omicron. By testing an array of mutated spike receptor binding domain (RBD) proteins, cell-expressed spike proteins from VOCs, and neutralization of SARS-CoV-2 VOCs as pseudoviruses, or as the authentic viruses in culture, we show that mAbs directed against the ACE2 binding site (ACE2bs) are more sensitive to viral evolution compared to anti-RBD non-ACE2bs mAbs, two of which retain their potency against all VOCs tested. At the second part of our study, we reveal the neutralization mechanisms at high molecular resolution of two anti-SARS-CoV-2 neutralizing mAbs by structural characterization. We solve the structures of the Delta-neutralizing ACE2bs mAb TAU-2303 with the SARS-CoV-2 spike trimer and RBD at 4.5 A and 2.42 A resolutions, respectively, revealing a similar mode of binding to that between the RBD and ACE2. Furthermore, we provide five additional structures (at resolutions of 4.7 A, 7.3 A, 6.4 A, 3.3 A, and 6.1 A) of a second antibody, TAU-2212, complexed with the SARS-CoV-2 spike trimer. TAU-2212 binds an exclusively quaternary epitope, and exhibits a unique, flexible mode of neutralization that involves transitioning between five different conformations, with both arms of the antibody recruited for cross linking intra- and inter-spike RBD subunits. Our study provides additional mechanistic understanding about how antibodies neutralize SARS-CoV-2 and its emerging variants and provides insights on the likelihood of reinfections.
		+
		+	Conformational flexibility in neutralization of SARS-CoV-2 by naturally elicited anti-SARS-CoV-2 antibodies.,Li R, Mor M, Ma B, Clark AE, Alter J, Werbner M, Lee JC, Leibel SL, Carlin AF, Dessau M, Gal-Tanamy M, Croker BA, Xiang Y, Freund NT Commun Biol. 2022 Aug 5;5(1):789. doi: 10.1038/s42003-022-03739-5. PMID:35931732<ref>PMID:35931732</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7wbz" style="background-color:#fffaf0;"></div>
		+	== 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: Ma B]]
		+	[[Category: Xiang Y]]

OCA at 06:38, 31 August 2022

OCA — Wed, 31 Aug 2022 06:38:12 GMT

←Older revision		Revision as of 06:38, 31 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7wbz ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7wbz' size='340' side='right'caption='[[7wbz]]' scene=''>
-	~~Authors~~: ~~Xiang, Y~~.~~, Ma, B~~.	+	== 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 SARS~~-~~Cov-2 RBD in complex with Fab 2303~~	+	</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=7wbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wbz OCA], [https://pdbe.org/7wbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wbz RCSB], [https://www.ebi.ac.uk/pdbsum/7wbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wbz ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Ma, B~~]]	+	__TOC__
-	[[Category: ~~Xiang, Y~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 09:24, 5 January 2022

OCA — Wed, 05 Jan 2022 09:24:29 GMT

←Older revision		Revision as of 09:24, 5 January 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

-	Authors: Xiang, Y., Ma, B~~., Freund, N~~.	+	Authors: Xiang, Y., Ma, B.

	Description: Crystal structure of the SARS-Cov-2 RBD in complex with Fab 2303		Description: Crystal structure of the SARS-Cov-2 RBD in complex with Fab 2303
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Ma, B]]		[[Category: Ma, B]]
-	[[Category: Freund, N]]
	[[Category: Xiang, Y]]		[[Category: Xiang, Y]]

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

OCA — Wed, 29 Dec 2021 12:37:10 GMT

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

←Older revision

Revision as of 12:37, 29 December 2021

OCA: New page: '''Unreleased structure''' The entry 7wbz is ON HOLD Authors: Xiang, Y., Ma, B., Freund, N. Description: Crystal structure of the SARS-Cov-2 RBD in complex with Fab 2303 [[Category: Un...

OCA — Wed, 29 Dec 2021 12:37:08 GMT

New page: '''Unreleased structure''' The entry 7wbz is ON HOLD Authors: Xiang, Y., Ma, B., Freund, N. Description: Crystal structure of the SARS-Cov-2 RBD in complex with Fab 2303 [[Category: Un...

New page

'''Unreleased structure'''

The entry 7wbz is ON HOLD

Authors: Xiang, Y., Ma, B., Freund, N.

Description: Crystal structure of the SARS-Cov-2 RBD in complex with Fab 2303
[[Category: Unreleased Structures]]
[[Category: Ma, B]]
[[Category: Freund, N]]
[[Category: Xiang, Y]]