Scholars@Duke

Controlling the SARS-CoV-2 spike glycoprotein conformation.

Publication ,  Journal Article
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
Published in: Nat Struct Mol Biol
October 2020
Published version (DOI) Link to item

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.

Duke Scholars

Rory Henderson
Author Rory Henderson Medicine, Duke Human Vaccine Institute
Mario-Juan Borgnia
Author Mario-Juan Borgnia Biochemistry
Barton Ford Haynes
Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute
Priyamvada Acharya
Author Priyamvada Acharya Surgery, Surgical Sciences
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Published In

Nat Struct Mol Biol

DOI

10.1038/s41594-020-0479-4

EISSN

1545-9985

Publication Date

October 2020

Volume

27

Issue

10

Start / End Page

925 / 933

Location

United States

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • Protein Subunits
  • Protein Domains
  • Protein Conformation
  • Mutation
  • Models, Molecular
  • Microscopy, Electron
  • Developmental Biology
  • Cryoelectron Microscopy
  • Biophysics
 

Citation

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Chicago
ICMJE
MLA
NLM
Henderson, R., Edwards, R. J., Mansouri, K., Janowska, K., Stalls, V., Gobeil, S. M. C., … Acharya, P. (2020). Controlling the SARS-CoV-2 spike glycoprotein conformation. Nat Struct Mol Biol, 27(10), 925–933. https://doi.org/10.1038/s41594-020-0479-4
Henderson, Rory, Robert J. Edwards, Katayoun Mansouri, Katarzyna Janowska, Victoria Stalls, Sophie M. C. Gobeil, Megan Kopp, et al. “Controlling the SARS-CoV-2 spike glycoprotein conformation.” Nat Struct Mol Biol 27, no. 10 (October 2020): 925–33. https://doi.org/10.1038/s41594-020-0479-4.
Henderson R, Edwards RJ, Mansouri K, Janowska K, Stalls V, Gobeil SMC, et al. Controlling the SARS-CoV-2 spike glycoprotein conformation. Nat Struct Mol Biol. 2020 Oct;27(10):925–33.
Henderson, Rory, et al. “Controlling the SARS-CoV-2 spike glycoprotein conformation.” Nat Struct Mol Biol, vol. 27, no. 10, Oct. 2020, pp. 925–33. Pubmed, doi:10.1038/s41594-020-0479-4.
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 Oct;27(10):925–933.

Published In

Nat Struct Mol Biol

DOI

10.1038/s41594-020-0479-4

EISSN

1545-9985

Publication Date

October 2020

Volume

27

Issue

10

Start / End Page

925 / 933

Location

United States

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • Protein Subunits
  • Protein Domains
  • Protein Conformation
  • Mutation
  • Models, Molecular
  • Microscopy, Electron
  • Developmental Biology
  • Cryoelectron Microscopy
  • Biophysics