6zp2
From Proteopedia
(Difference between revisions)
m (Protected "6zp2" [edit=sysop:move=sysop]) |
|||
| Line 1: | Line 1: | ||
==Structure of SARS-CoV-2 Spike Protein Trimer (K986P, V987P, single Arg S1/S2 cleavage site) in Locked State== | ==Structure of SARS-CoV-2 Spike Protein Trimer (K986P, V987P, single Arg S1/S2 cleavage site) in Locked State== | ||
| - | <StructureSection load='6zp2' size='340' side='right'caption='[[6zp2]]' scene=''> | + | <StructureSection load='6zp2' size='340' side='right'caption='[[6zp2]], [[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=6ZP2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZP2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6zp2]] 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=6ZP2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZP2 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=6zp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zp2 OCA], [http://pdbe.org/6zp2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zp2 RCSB], [http://www.ebi.ac.uk/pdbsum/6zp2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zp2 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=EIC:LINOLEIC+ACID'>EIC</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 ([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=6zp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zp2 OCA], [http://pdbe.org/6zp2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zp2 RCSB], [http://www.ebi.ac.uk/pdbsum/6zp2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zp2 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 spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. It exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor-binding site and, subsequently, from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S-protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S that allow the production of thermostable, disulfide-bonded S-protein trimers that are trapped in the closed, prefusion state. Structures of the disulfide-stabilized and non-disulfide-stabilized proteins reveal distinct closed and locked conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen. | ||
| + | |||
| + | A thermostable, closed SARS-CoV-2 spike protein trimer.,Xiong X, Qu K, Ciazynska KA, Hosmillo M, Carter AP, Ebrahimi S, Ke Z, Scheres SHW, Bergamaschi L, Grice GL, Zhang Y, Nathan JA, Baker S, James LC, Baxendale HE, Goodfellow I, Doffinger R, Briggs JAG Nat Struct Mol Biol. 2020 Jul 31. pii: 10.1038/s41594-020-0478-5. doi:, 10.1038/s41594-020-0478-5. PMID:32737467<ref>PMID:32737467</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6zp2" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: 2019-ncov]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Briggs | + | [[Category: Briggs, J A.G]] |
| - | [[Category: Qu K]] | + | [[Category: Qu, K]] |
| - | [[Category: Scheres | + | [[Category: Scheres, S H.W]] |
| - | [[Category: Xiong X]] | + | [[Category: Xiong, X]] |
| + | [[Category: Coronavirus]] | ||
| + | [[Category: Covid-19]] | ||
| + | [[Category: Membrane fusion]] | ||
| + | [[Category: Receptor binding]] | ||
| + | [[Category: S antigen]] | ||
| + | [[Category: S protein]] | ||
| + | [[Category: Sars-cov-2]] | ||
| + | [[Category: Spike protein]] | ||
| + | [[Category: Vaccine design]] | ||
| + | [[Category: Viral protein]] | ||
Revision as of 10:11, 12 August 2020
Structure of SARS-CoV-2 Spike Protein Trimer (K986P, V987P, single Arg S1/S2 cleavage site) in Locked State
| |||||||||||
