Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.
Zhang, X., Li, Z., Zhang, Y., Liu, Y., Wang, J., Liu, B., Chen, Q., Wang, Q., Fu, L., Wang, P., Zhong, X., Jin, L., Yan, Q., Chen, L., He, J., Zhao, J., Xiong, X.(2023) Life Sci Alliance 6
- PubMed: 37402591
- DOI: https://doi.org/10.26508/lsa.202201796
- Primary Citation of Related Structures:
8H0X, 8H0Y, 8H0Z, 8H10, 8H11, 8H12, 8H13, 8H14, 8H15, 8H16 - PubMed 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.
Organizational Affiliation:
State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.