Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes

Life Sci Alliance. 2023 Jul 4;6(9):e202201796. doi: 10.26508/lsa.202201796. Print 2023 Sep.

Abstract

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures with other available spike structures of SARS-related CoVs to identify conserved features and discuss their possible functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Cryoelectron Microscopy
  • Disulfides / chemistry
  • Humans
  • Models, Molecular
  • SARS-CoV-2*

Substances

  • spike protein, SARS-CoV-2
  • Disulfides

Associated data

  • PDB/5X58
  • PDB/7XTZ
  • PDB/7XU2
  • PDB/7XU3
  • PDB/6XM5
  • PDB/7BBH
  • PDB/7CN8
  • PDB/7CN4
  • PDB/6ZGF
  • PDB/5X5B
  • PDB/5XLR
  • PDB/6ACC
  • PDB/6ACD
  • PDB/6CRW
  • PDB/8H14
  • PDB/7LM9
  • PDB/8DW2
  • PDB/8H0X
  • PDB/8H0Y
  • PDB/8H0Z
  • PDB/8H10
  • PDB/8H11
  • PDB/8H12
  • PDB/8H13
  • PDB/8H15
  • PDB/8H16