Controlling the SARS-CoV-2 spike glycoprotein conformation
By R. Henderson, R. Edwards, K. Mansouri, Katarzyna Janowska, V. Stalls, S. Gobeil, Megan Kopp, Dapeng Li, R. Parks, A. Hsu and 3 more. Nature Structural & Molecular Biology, 2020
301 citations recorded by the source corpus.
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. The SARS-CoV-2 spike glycoprotein is flexible, and its receptor-binding domain (RBD) fluctuates between up or down conformations. Mutations engineered into the spike ectodomain either lock the RBD in the down state or make it adopt the up conformation more readily.
Subfields: Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/93f6fe2fbef8bb6a51828cb3a3c0e912772d26ca
Citations in the corpus
- Molecular Architecture of the SARS-CoV-2 Virus (2020, unknown): “The “RBD down”, “one RBD up” and “two-RBD up” conformations have been observed in recombinantly expressed S proteins of SARS-CoV-2 (Henderson et al., 2020; Walls et al., 2020; Wrapp et al., 2020).”
- Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, unknown): “Several reports of stabilized prefusion SARS-CoV-2 S variants provide promising antigens that can be used to test this hypothesis (Henderson et al., 2020; Hsieh et al., 2020; McCallum et al., 2020; Xiong et al., 2020).”