Controlling the SARS-CoV-2 Spike Glycoprotein Conformation

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2020 Jul 24

PMID 32699321

Citations 243

Authors

Rory Henderson

Robert J Edwards

Katayoun Mansouri

Katarzyna Janowska

Victoria Stalls

Sophie M C Gobeil

Megan Kopp

Dapeng Li

Rob Parks

Allen L Hsu

Mario J Borgnia

Barton F Haynes

Priyamvada Acharya

Affiliations

Soon will be listed here.

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.

Citing Articles

Production and cryo-electron microscopy structure of an internally tagged SARS-CoV-2 spike ecto-domain construct.

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Exploring the effects of N234 and N343 linked glycans to SARS CoV 2 spike protein pocket accessibility using Gaussian accelerated molecular dynamics simulations.

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The effect of cysteine oxidation on conformational changes of SARS-CoV-2 spike protein using atomistic simulations.

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Mutational Scanning and Binding Free Energy Computations of the SARS-CoV-2 Spike Complexes with Distinct Groups of Neutralizing Antibodies: Energetic Drivers of Convergent Evolution of Binding Affinity and Immune Escape Hotspots.

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Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies.

Alshahrani M, Parikh V, Foley B, Raisinghani N, Verkhivker G Biomolecules. 2025; 15(2).

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