6x2b: Difference between revisions
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==SARS-CoV-2 u1S2q 2 RBD Up Spike Protein Trimer== | ==SARS-CoV-2 u1S2q 2 RBD Up Spike Protein Trimer== | ||
<StructureSection load='6x2b' size='340' side='right'caption='[[6x2b]]' scene=''> | <StructureSection load='6x2b' size='340' side='right'caption='[[6x2b]], [[Resolution|resolution]] 3.60Å' 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=6X2B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6X2B FirstGlance]. <br> | <table><tr><td colspan='2'>[[6x2b]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X2B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6X2B 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=6x2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x2b OCA], [http://pdbe.org/6x2b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6x2b RCSB], [http://www.ebi.ac.uk/pdbsum/6x2b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6x2b ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S, 2 ([http://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'>[http://proteopedia.org/fgij/fg.htm?mol=6x2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x2b OCA], [http://pdbe.org/6x2b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6x2b RCSB], [http://www.ebi.ac.uk/pdbsum/6x2b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6x2b ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://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 == | |||
The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available beta-CoV S-protein structures. We found that despite overall similarity in domain organization, different beta-CoV strains display distinct S-protein configurations. Based on this analysis, we developed two soluble ectodomain constructs in which the highly immunogenic and mobile receptor binding domain (RBD) is locked in either the all-RBDs 'down' position or is induced to display a previously unobserved in SARS-CoV-2 2-RBDs 'up' configuration. These results demonstrate that the conformation of the S-protein can be controlled via rational design and provide a framework for the development of engineered coronavirus spike proteins for vaccine applications. | |||
Controlling the SARS-CoV-2 Spike Glycoprotein Conformation.,Henderson R, Edwards RJ, Mansouri K, Janowska K, Stalls V, Gobeil S, Kopp M, Hsu A, Borgnia M, Parks R, Haynes BF, Acharya P bioRxiv. 2020 May 18. doi: 10.1101/2020.05.18.102087. PMID:32511343<ref>PMID:32511343</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6x2b" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: 2019-ncov]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Acharya P]] | [[Category: Acharya, P]] | ||
[[Category: Henderson R]] | [[Category: Henderson, R]] | ||
[[Category: Trimer]] | |||
[[Category: Viral protein]] | |||
Revision as of 10:17, 25 June 2020
SARS-CoV-2 u1S2q 2 RBD Up Spike Protein TrimerSARS-CoV-2 u1S2q 2 RBD Up Spike Protein Trimer
Structural highlights
Function[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][1] [2] [3] 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] Publication Abstract from PubMedThe coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available beta-CoV S-protein structures. We found that despite overall similarity in domain organization, different beta-CoV strains display distinct S-protein configurations. Based on this analysis, we developed two soluble ectodomain constructs in which the highly immunogenic and mobile receptor binding domain (RBD) is locked in either the all-RBDs 'down' position or is induced to display a previously unobserved in SARS-CoV-2 2-RBDs 'up' configuration. These results demonstrate that the conformation of the S-protein can be controlled via rational design and provide a framework for the development of engineered coronavirus spike proteins for vaccine applications. Controlling the SARS-CoV-2 Spike Glycoprotein Conformation.,Henderson R, Edwards RJ, Mansouri K, Janowska K, Stalls V, Gobeil S, Kopp M, Hsu A, Borgnia M, Parks R, Haynes BF, Acharya P bioRxiv. 2020 May 18. doi: 10.1101/2020.05.18.102087. PMID:32511343[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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