Controlling the SARS-CoV-2 spike glycoprotein conformation.
Nat Struct Mol Biol
; 27(10): 925-933, 2020 10.
Article
in English
| MEDLINE | ID: covidwho-662441
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
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 ß-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different ß-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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spike Glycoprotein, Coronavirus
Type of study:
Experimental Studies
Topics:
Vaccines
Language:
English
Journal:
Nat Struct Mol Biol
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
S41594-020-0479-4
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