7c8w - Revision history

OCA at 16:00, 29 November 2023

2023-11-29T16:00:30Z

←Older revision		Revision as of 16:00, 29 November 2023
Line 3:		Line 3:
	<StructureSection load='7c8w' size='340' side='right'caption='[[7c8w]], [[Resolution\|resolution]] 2.77Å' scene=''>		<StructureSection load='7c8w' size='340' side='right'caption='[[7c8w]], [[Resolution\|resolution]] 2.77Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7c8w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~2019-ncov 2019-ncov~~] and [https://en.wikipedia.org/wiki/~~Synthetic_construct_sequences~~ Synthetic construct ~~sequences~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C8W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7c8w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C8W FirstGlance]. <br>
-	</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=~~FUC~~:~~ALPHA-L-FUCOSE~~'>~~FUC~~</scene>, <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]] 2.77Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S, 2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7c8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c8w OCA], [https://pdbe.org/7c8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c8w RCSB], [https://www.ebi.ac.uk/pdbsum/7c8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c8w 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=7c8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c8w OCA], [https://pdbe.org/7c8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c8w RCSB], [https://www.ebi.ac.uk/pdbsum/7c8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c8w 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 ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Synthetic construct ~~sequences~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
-	[[Category: Cai, H]]	+	[[Category: Synthetic construct]]
-	[[Category: Li, D]]	+	[[Category: Cai H]]
-	[[Category: Li, T]]	+	[[Category: Li D]]
-	[[Category: Qin, W]]	+	[[Category: Li T]]
-	[[Category: Yao, H]]	+	[[Category: Qin W]]
-	~~[[Category: Coronavirus]]~~	+	[[Category: Yao H]]
-	~~[[Category: Covid-19]]~~	+
-	~~[[Category: Nanobody]]~~	+
-	~~[[Category: Neutralizing antibody]]~~	+
-	~~[[Category: Protein binding]]~~	+
-	~~[[Category: Receptor binding protein]]~~	+
-	~~[[Category: S protein]]~~	+
-	~~[[Category: Sars-cov-2]]~~	+
-	~~[[Category: Synthetic antibody]]~~	+
-	~~[[Category: Vhh~~]]	+

OCA at 10:42, 5 January 2022

2022-01-05T10:42:05Z

←Older revision		Revision as of 10:42, 5 January 2022
Line 10:		Line 10:
	== 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;">
		+	== Publication Abstract from PubMed ==
		+	SARS-CoV-2, the causative agent of COVID-19(1), features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein(1-6). Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics(7-17). Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic nanobodies (sybodies) against RBD by in vitro selection using three libraries. The best sybody, MR3 binds to RBD with high affinity (KD = 1.0 nM) and displays high neutralization activity against SARS-CoV-2 pseudoviruses (IC50 = 0.42 mug mL(-1)). Structural, biochemical, and biological characterization suggests a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency have been generated by structure-based design, biparatopic construction, and divalent engineering. Two divalent forms of MR3 protect hamsters from clinical signs after live virus challenge and a single dose of the Fc-fusion construct of MR3 reduces viral RNA load by 6 Log10. Our results pave the way for the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid development of targeted medical interventions during an outbreak.
		+
		+	A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection.,Li T, Cai H, Yao H, Zhou B, Zhang N, van Vlissingen MF, Kuiken T, Han W, GeurtsvanKessel CH, Gong Y, Zhao Y, Shen Q, Qin W, Tian XX, Peng C, Lai Y, Wang Y, Hutter CAJ, Kuo SM, Bao J, Liu C, Wang Y, Richard AS, Raoul H, Lan J, Seeger MA, Cong Y, Rockx B, Wong G, Bi Y, Lavillette D, Li D Nat Commun. 2021 Jul 30;12(1):4635. doi: 10.1038/s41467-021-24905-z. PMID:34330908<ref>PMID:34330908</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7c8w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:01, 10 March 2021

2021-03-10T18:01:06Z

←Older revision		Revision as of 18:01, 10 March 2021
Line 1:		Line 1:

	==Structure of sybody MR17 in complex with the SARS-CoV-2 S receptor-binding domain (RBD)==		==Structure of sybody MR17 in complex with the SARS-CoV-2 S receptor-binding domain (RBD)==
-	<StructureSection load='7c8w' size='340' side='right'caption='[[7c8w]]' scene=''>	+	<StructureSection load='7c8w' size='340' side='right'caption='[[7c8w]], [[Resolution\|resolution]] 2.77Å' 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=7C8W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7C8W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7c8w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/2019-ncov 2019-ncov] and [https://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C8W FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7c8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c8w OCA], [~~http~~://pdbe.org/7c8w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7c8w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7c8w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7c8w 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S, 2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</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=7c8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c8w OCA], [https://pdbe.org/7c8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c8w RCSB], [https://www.ebi.ac.uk/pdbsum/7c8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c8w 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]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cai H]]	+	[[Category: Synthetic construct sequences]]
-	[[Category: Li D]]	+	[[Category: Cai, H]]
-	[[Category: Li T]]	+	[[Category: Li, D]]
-	[[Category: Qin W]]	+	[[Category: Li, T]]
-	[[Category: Yao H]]	+	[[Category: Qin, W]]
		+	[[Category: Yao, H]]
		+	[[Category: Coronavirus]]
		+	[[Category: Covid-19]]
		+	[[Category: Nanobody]]
		+	[[Category: Neutralizing antibody]]
		+	[[Category: Protein binding]]
		+	[[Category: Receptor binding protein]]
		+	[[Category: S protein]]
		+	[[Category: Sars-cov-2]]
		+	[[Category: Synthetic antibody]]
		+	[[Category: Vhh]]

OCA at 06:34, 25 June 2020

2020-06-25T06:34:05Z

←Older revision		Revision as of 06:34, 25 June 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7c8w is ON HOLD~~	+	==Structure of sybody MR17 in complex with the SARS-CoV-2 S receptor-binding domain (RBD)==
-		+	<StructureSection load='7c8w' size='340' side='right'caption='[[7c8w]]' scene=''>
-	~~Authors: Li, T., Cai, H., Yao, H., Qin, W., Li, D.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C8W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C8W FirstGlance]. <br>
-	~~Description:~~ Structure of sybody MR17 in complex with the SARS-CoV-2 S ~~Receptor Binding~~ domain (RBD)	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c8w OCA], [http://pdbe.org/7c8w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c8w RCSB], [http://www.ebi.ac.uk/pdbsum/7c8w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c8w ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Li, D~~]]	+	__TOC__
-	[[Category: Li~~, T~~]]	+	</StructureSection>
-	[[Category: ~~Qin, W~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Yao, H~~]]	+	[[Category: Cai H]]
-	[[Category: ~~Cai,~~ H]]	+	[[Category: Li D]]
		+	[[Category: Li T]]
		+	[[Category: Qin W]]
		+	[[Category: Yao H]]

OCA: Protected "7c8w" [edit=sysop:move=sysop]

2020-06-10T05:19:14Z

Protected "7c8w" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:19, 10 June 2020

OCA: New page: '''Unreleased structure''' The entry 7c8w is ON HOLD Authors: Li, T., Cai, H., Yao, H., Qin, W., Li, D. Description: Structure of sybody MR17 in complex with the SARS-CoV-2 S Receptor ...

2020-06-10T05:19:13Z

New page: '''Unreleased structure''' The entry 7c8w is ON HOLD Authors: Li, T., Cai, H., Yao, H., Qin, W., Li, D. Description: Structure of sybody MR17 in complex with the SARS-CoV-2 S Receptor ...

New page

'''Unreleased structure'''

The entry 7c8w is ON HOLD

Authors: Li, T., Cai, H., Yao, H., Qin, W., Li, D.

Description: Structure of sybody MR17 in complex with the SARS-CoV-2 S Receptor Binding domain (RBD)
[[Category: Unreleased Structures]]
[[Category: Li, D]]
[[Category: Li, T]]
[[Category: Qin, W]]
[[Category: Yao, H]]
[[Category: Cai, H]]