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6x2a

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Revision as of 07:43, 30 September 2020

SARS-CoV-2 u1S2q 1 Up RBD Spike Protein Trimer

Structural highlights

6x2a 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.
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 coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, 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. Despite an overall similarity in domain organization, we found that S-proteins from different beta-CoVs display distinct configurations. Based on this analysis, we developed two soluble ectodomain constructs for the SARS-CoV-2 S-protein, in which the highly immunogenic and mobile receptor binding domain (RBD) is either locked in the all-RBDs 'down' position or adopts 'up' state conformations more readily than the wild-type S-protein. These results demonstrate that the conformation of the S-protein can be controlled via rational design and can provide a framework for the development of engineered CoV S-proteins for vaccine applications.

Controlling the SARS-CoV-2 spike glycoprotein conformation.,Henderson R, Edwards RJ, Mansouri K, Janowska K, Stalls V, Gobeil SMC, Kopp M, Li D, Parks R, Hsu AL, Borgnia MJ, Haynes BF, Acharya P Nat Struct Mol Biol. 2020 Jul 22. pii: 10.1038/s41594-020-0479-4. doi:, 10.1038/s41594-020-0479-4. PMID:32699321^[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
↑ Henderson R, Edwards RJ, Mansouri K, Janowska K, Stalls V, Gobeil SMC, Kopp M, Li D, Parks R, Hsu AL, Borgnia MJ, Haynes BF, Acharya P. Controlling the SARS-CoV-2 spike glycoprotein conformation. Nat Struct Mol Biol. 2020 Jul 22. pii: 10.1038/s41594-020-0479-4. doi:, 10.1038/s41594-020-0479-4. PMID:32699321 doi:http://dx.doi.org/10.1038/s41594-020-0479-4

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6x2a"

@@ Line 11: / Line 11: @@
 <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.
+The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, 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. Despite an overall similarity in domain organization, we found that S-proteins from different beta-CoVs display distinct configurations. Based on this analysis, we developed two soluble ectodomain constructs for the SARS-CoV-2 S-protein, in which the highly immunogenic and mobile receptor binding domain (RBD) is either locked in the all-RBDs 'down' position or adopts 'up' state conformations more readily than the wild-type S-protein. These results demonstrate that the conformation of the S-protein can be controlled via rational design and can provide a framework for the development of engineered CoV S-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>
+Controlling the SARS-CoV-2 spike glycoprotein conformation.,Henderson R, Edwards RJ, Mansouri K, Janowska K, Stalls V, Gobeil SMC, Kopp M, Li D, Parks R, Hsu AL, Borgnia MJ, Haynes BF, Acharya P Nat Struct Mol Biol. 2020 Jul 22. pii: 10.1038/s41594-020-0479-4. doi:, 10.1038/s41594-020-0479-4. PMID:32699321<ref>PMID:32699321</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

6x2a

From Proteopedia

Revision as of 07:43, 30 September 2020

SARS-CoV-2 u1S2q 1 Up RBD Spike Protein Trimer

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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