6zoz

From Proteopedia

(Difference between revisions)

Revision as of 07:23, 2 March 2022

Structure of Disulphide-stabilized SARS-CoV-2 Spike Protein Trimer (x1 disulphide-bond mutant, S383C, D985C, K986P, V987P, single Arg S1/S2 cleavage site) in Locked State

Structural highlights

6zoz is a 3 chain structure with sequence from 2019-ncov. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	S, 2 (2019-nCoV)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020 Feb 19. pii: science.abb2507. doi: 10.1126/science.abb2507. PMID:32075877 doi:http://dx.doi.org/10.1126/science.abb2507
↑ Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020, Mar 5. PMID:32142651 doi:http://dx.doi.org/10.1016/j.cell.2020.02.052
↑ Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020 Mar 6. pii: S0092-8674(20)30262-2. doi: 10.1016/j.cell.2020.02.058. PMID:32155444 doi:http://dx.doi.org/10.1016/j.cell.2020.02.058
↑ 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. A thermostable, closed SARS-CoV-2 spike protein trimer. Nat Struct Mol Biol. 2020 Jul 31. pii: 10.1038/s41594-020-0478-5. doi:, 10.1038/s41594-020-0478-5. PMID:32737467 doi:http://dx.doi.org/10.1038/s41594-020-0478-5

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/6zoz"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6zoz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZOZ 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BLA:BILIVERDINE+IX+ALPHA'>BLA</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=6zoz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zoz OCA], [https://pdbe.org/6zoz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zoz RCSB], [https://www.ebi.ac.uk/pdbsum/6zoz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zoz ProSAT]</span></td></tr>

6zoz

From Proteopedia

Revision as of 07:23, 2 March 2022

Structure of Disulphide-stabilized SARS-CoV-2 Spike Protein Trimer (x1 disulphide-bond mutant, S383C, D985C, K986P, V987P, single Arg S1/S2 cleavage site) in Locked State

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox