tetano
Editor, Senior Moderator
EMBO J
. 2024 Nov 14.
doi: 10.1038/s44318-024-00303-1. Online ahead of print. Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants
Zunlong Ke[SUP] 1 2 3 [/SUP], Thomas P Peacock[SUP] 4 5 [/SUP], Jonathan C Brown[SUP] 4 [/SUP], Carol M Sheppard[SUP] 4 [/SUP], Tristan I Croll[SUP] 6 7 [/SUP], Abhay Kotecha[SUP] 8 [/SUP], Daniel H Goldhill[SUP] 4 9 [/SUP], Wendy S Barclay[SUP] 4 [/SUP], John A G Briggs[SUP] 10 11 [/SUP]
Affiliations
The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins, which are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S protein from SARS-CoV-2 variants has revealed this structural adaptation at high resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, "in-situ" high-resolution S structures, and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Taken together, our data are consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of the S protein.
Keywords: Coronavirus; Cryo-electron Tomography; Membrane Fusion Protein; Virus Evolution; Virus Structure.
. 2024 Nov 14.
doi: 10.1038/s44318-024-00303-1. Online ahead of print. Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants
Zunlong Ke[SUP] 1 2 3 [/SUP], Thomas P Peacock[SUP] 4 5 [/SUP], Jonathan C Brown[SUP] 4 [/SUP], Carol M Sheppard[SUP] 4 [/SUP], Tristan I Croll[SUP] 6 7 [/SUP], Abhay Kotecha[SUP] 8 [/SUP], Daniel H Goldhill[SUP] 4 9 [/SUP], Wendy S Barclay[SUP] 4 [/SUP], John A G Briggs[SUP] 10 11 [/SUP]
Affiliations
- PMID: 39543395
- DOI: 10.1038/s44318-024-00303-1
The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins, which are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S protein from SARS-CoV-2 variants has revealed this structural adaptation at high resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, "in-situ" high-resolution S structures, and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Taken together, our data are consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of the S protein.
Keywords: Coronavirus; Cryo-electron Tomography; Membrane Fusion Protein; Virus Evolution; Virus Structure.