tetano
Editor, Senior Moderator
Nat Struct Mol Biol
. 2020 Jul 22.
doi: 10.1038/s41594-020-0479-4. Online ahead of print.
Controlling the SARS-CoV-2 spike glycoprotein conformation
Rory Henderson[SUP] 1 2 [/SUP], Robert J Edwards[SUP] 3 4 [/SUP], Katayoun Mansouri[SUP] 3 [/SUP], Katarzyna Janowska[SUP] 3 [/SUP], Victoria Stalls[SUP] 3 [/SUP], Sophie M C Gobeil[SUP] 3 [/SUP], Megan Kopp[SUP] 3 [/SUP], Dapeng Li[SUP] 3 [/SUP], Rob Parks[SUP] 3 [/SUP], Allen L Hsu[SUP] 5 [/SUP], Mario J Borgnia[SUP] 5 [/SUP], Barton F Haynes[SUP] 3 4 6 [/SUP], Priyamvada Acharya[SUP] 7 8 [/SUP]
Affiliations
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 β-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different β-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.
. 2020 Jul 22.
doi: 10.1038/s41594-020-0479-4. Online ahead of print.
Controlling the SARS-CoV-2 spike glycoprotein conformation
Rory Henderson[SUP] 1 2 [/SUP], Robert J Edwards[SUP] 3 4 [/SUP], Katayoun Mansouri[SUP] 3 [/SUP], Katarzyna Janowska[SUP] 3 [/SUP], Victoria Stalls[SUP] 3 [/SUP], Sophie M C Gobeil[SUP] 3 [/SUP], Megan Kopp[SUP] 3 [/SUP], Dapeng Li[SUP] 3 [/SUP], Rob Parks[SUP] 3 [/SUP], Allen L Hsu[SUP] 5 [/SUP], Mario J Borgnia[SUP] 5 [/SUP], Barton F Haynes[SUP] 3 4 6 [/SUP], Priyamvada Acharya[SUP] 7 8 [/SUP]
Affiliations
- PMID: 32699321
- DOI: 10.1038/s41594-020-0479-4
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 β-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different β-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.