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.; Chen, L.; He, J.; Zhao, J.; Xiong, X.

doi:10.1101/2022.10.14.512296

bioRxiv · 10.1101/2022.10.14.512296

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.·Chen, L.·He, J.·Zhao, J.·Xiong, X.

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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. The locked conformations feature tightly packed trimers with structural elements incompatible with RBD in "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably due to their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. Intriguingly, locked conformations were the only conformations captured for S proteins of bat and pangolin origin SARS-related coronaviruses. 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 to other available spike structures of Sarbecoviruses to identify conserved features and discuss their possible functions.

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Zhang, X., Li, Z., Zhang, Y., Liu, Y., Wang, J., Liu, B., Chen, Q., Wang, Q., Fu, L., Wang, P., Zhong, X., Jin, L., Chen, L., He, J., Zhao, J., Xiong, X.. 2022-10-16. Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.. https://doi.org/10.1101/2022.10.14.512296

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