Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published March 24, 2023 | Submitted
Report Open

Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk and enhanced NTD dynamics


SARS-CoV-2 emergent variants are characterized by increased transmissibility and each show multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track correlative changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in Omicron BA.1 S traced through Alpha S and Delta S variants. Stabilization preceded progressive enhancement in dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from specific S mutations detail the evolutionary trajectory of S protein in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. Startup funding from the Pennsylvania State University (PSU) to GSA. We thank Rosa Viner (Thermo Scientific, San Jose, CA) for spike protein glycan analysis. Data and Materials availability: Mass Spectrometry data: ProteomeXchange Consortium via the PRIDE partner repository. All data is available in the main text and supplemental information. Information on recombinant proteins and reagents is available upon request. The authors have declared no competing interest.

Attached Files

Submitted - 2022.08.26.505369v1.full.pdf


Files (12.5 MB)
Name Size Download all
12.5 MB Preview Download

Additional details

August 20, 2023
December 22, 2023