8dlr - Revision history

OCA at 14:29, 6 November 2024

2024-11-06T14:29:33Z

← Older revision		Revision as of 14:29, 6 November 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8dlr]] 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=8DLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DLR FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dlr]] 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=8DLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DLR 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">Electron Microscopy, [[Resolution\|Resolution]] 2.51Å</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=8dlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dlr OCA], [https://pdbe.org/8dlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dlr RCSB], [https://www.ebi.ac.uk/pdbsum/8dlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dlr 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=8dlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dlr OCA], [https://pdbe.org/8dlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dlr RCSB], [https://www.ebi.ac.uk/pdbsum/8dlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dlr 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 ==
	Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (VH ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants.		Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V(H) ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants.

	SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization.,Mannar D, Saville JW, Sun Z, Zhu X, Marti MM, Srivastava SS, Berezuk AM, Zhou S, Tuttle KS, Sobolewski MD, Kim A, Treat BR, Da Silva Castanha PM, Jacobs JL, Barratt-Boyes SM, Mellors JW, Dimitrov DS, Li W, Subramaniam S Nat Commun. 2022 Aug 18;13(1):4696. doi: 10.1038/s41467-022-32262-8. PMID:35982054<ref>PMID:35982054</ref>		SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization.,Mannar D, Saville JW, Sun Z, Zhu X, Marti MM, Srivastava SS, Berezuk AM, Zhou S, Tuttle KS, Sobolewski MD, Kim A, Treat BR, Da Silva Castanha PM, Jacobs JL, Barratt-Boyes SM, Mellors JW, Dimitrov DS, Li W, Subramaniam S Nat Commun. 2022 Aug 18;13(1):4696. doi: 10.1038/s41467-022-32262-8. PMID:35982054<ref>PMID:35982054</ref>
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	</div>		</div>
	<div class="pdbe-citations 8dlr" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 8dlr" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Antibody 3D structures\|Antibody 3D structures]]
			*[[Spike protein 3D structures\|Spike protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:40, 7 September 2022

2022-09-07T19:40:34Z

← Older revision		Revision as of 19:40, 7 September 2022
Line 1:		Line 1:

	====		==Cryo-EM structure of SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4-8 (focused refinement of NTD and 4-8)==
	<StructureSection load='8dlr' size='340' side='right'caption='[[8dlr]]' scene=''>		<StructureSection load='8dlr' size='340' side='right'caption='[[8dlr]], [[Resolution\|resolution]] 2.51Å' 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'>[[8dlr]] 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=8DLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DLR 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=8dlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dlr OCA], [https://pdbe.org/8dlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dlr RCSB], [https://www.ebi.ac.uk/pdbsum/8dlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dlr 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=8dlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dlr OCA], [https://pdbe.org/8dlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dlr RCSB], [https://www.ebi.ac.uk/pdbsum/8dlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dlr 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 ==
			Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (VH ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants.

			SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization.,Mannar D, Saville JW, Sun Z, Zhu X, Marti MM, Srivastava SS, Berezuk AM, Zhou S, Tuttle KS, Sobolewski MD, Kim A, Treat BR, Da Silva Castanha PM, Jacobs JL, Barratt-Boyes SM, Mellors JW, Dimitrov DS, Li W, Subramaniam S Nat Commun. 2022 Aug 18;13(1):4696. doi: 10.1038/s41467-022-32262-8. PMID:35982054<ref>PMID:35982054</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 8dlr" 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: Berezuk AM]]
			[[Category: Mannar D]]
			[[Category: Saville JW]]
			[[Category: Srivastava SS]]
			[[Category: Subramaniam S]]
			[[Category: Tuttle KS]]
			[[Category: Zhou S]]
			[[Category: Zhu X]]

OCA at 06:40, 31 August 2022

2022-08-31T06:40:41Z

← Older revision		Revision as of 06:40, 31 August 2022
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 8dlr ~~is ON HOLD until Paper Publication~~		====
			<StructureSection load='8dlr' size='340' side='right'caption='[[8dlr]]' scene=''>
	~~Authors~~: ~~Zhu, X~~.~~, Mannar, D~~.~~, Saville, J~~.W.~~, Srivastava, S~~.S.~~, Berezuk, A~~.M.~~, Zhou, S~~., ~~Tuttle, K~~.S.~~, Subramaniam, S~~.		== 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 Gamma (P.1) spike protein in complex with Fab 4-8 (focused refinement of NTD and 4-8)~~		</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=8dlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dlr OCA], [https://pdbe.org/8dlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dlr RCSB], [https://www.ebi.ac.uk/pdbsum/8dlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dlr ProSAT]</span></td></tr>
	[~~[Category~~: ~~Unreleased Structures]~~]		</table>
	~~[[Category: Subramaniam~~, ~~S]]~~		__TOC__
	[~~[Category~~: ~~Saville, J~~.W]]		</StructureSection>
	~~[[Category: Zhou~~, ~~S]]~~		[[Category: Large Structures]]
	[~~[Category~~: ~~Srivastava, S~~.S]]		[[Category: Z-disk]]
	~~[[Category: Zhu~~, ~~X]]~~
	[~~[Category~~: ~~Tuttle, K~~.S]]
	[[Category: ~~Berezuk, A.M~~]]
	[[Category: ~~Mannar, D~~]]

OCA at 04:01, 10 August 2022

2022-08-10T04:01:05Z

← Older revision		Revision as of 04:01, 10 August 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8dlr is ON HOLD		The entry 8dlr is ON HOLD until Paper Publication

	Authors: Zhu, X., Mannar, D., Saville, J.W., Srivastava, S.S., Berezuk, A.M., Zhou, S., Tuttle, K.S., Subramaniam, S.		Authors: Zhu, X., Mannar, D., Saville, J.W., Srivastava, S.S., Berezuk, A.M., Zhou, S., Tuttle, K.S., Subramaniam, S.
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	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Subramaniam, S]]		[[Category: Subramaniam, S]]
	~~[[Category: Zhu, X]]~~
	~~[[Category: Tuttle, K.S]]~~
	~~[[Category: Mannar, D]]~~
	[[Category: Saville, J.W]]		[[Category: Saville, J.W]]
	[[Category: Zhou, S]]		[[Category: Zhou, S]]
	[[Category: Srivastava, S.S]]		[[Category: Srivastava, S.S]]
			[[Category: Zhu, X]]
			[[Category: Tuttle, K.S]]
	[[Category: Berezuk, A.M]]		[[Category: Berezuk, A.M]]
			[[Category: Mannar, D]]

OCA: Protected "8dlr" [edit=sysop:move=sysop]

2022-07-13T04:19:59Z

Protected "8dlr" [edit=sysop:move=sysop]

← Older revision	Revision as of 04:19, 13 July 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8dlr is ON HOLD Authors: Zhu, X., Mannar, D., Saville, J.W., Srivastava, S.S., Berezuk, A.M., Zhou, S., Tuttle, K.S., Subramaniam, S. Description: ...

2022-07-13T04:19:58Z

New page: '''Unreleased structure''' The entry 8dlr is ON HOLD Authors: Zhu, X., Mannar, D., Saville, J.W., Srivastava, S.S., Berezuk, A.M., Zhou, S., Tuttle, K.S., Subramaniam, S. Description: ...

New page

'''Unreleased structure'''

The entry 8dlr is ON HOLD

Authors: Zhu, X., Mannar, D., Saville, J.W., Srivastava, S.S., Berezuk, A.M., Zhou, S., Tuttle, K.S., Subramaniam, S.

Description: Cryo-EM structure of SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4-8 (focused refinement of NTD and 4-8)
[[Category: Unreleased Structures]]
[[Category: Subramaniam, S]]
[[Category: Zhu, X]]
[[Category: Tuttle, K.S]]
[[Category: Mannar, D]]
[[Category: Saville, J.W]]
[[Category: Zhou, S]]
[[Category: Srivastava, S.S]]
[[Category: Berezuk, A.M]]