8H0X

Structure of SARS-CoV-1 Spike Protein with Engineered x1 Disulfide (S370C and D967C), Locked-1 Conformation

Summary for 8H0X

• Entry DOI: 10.2210/pdb8h0x/pdb
• EMDB information: 34417
• Descriptor: Spike glycoprotein, LINOLEIC ACID, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: protein engineering, spike protein, sars-cov-1, sars-cov, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus
• Total number of polymer chains: 3
• Total formula weight: 421918.09

Authors

Zhang, X.,Li, Z.,Liu, Y.,Wang, J.,Fu, L.,Wang, P.,He, J.,Xiong, X. (deposition date: 2022-09-30, release date: 2022-11-09, Last modification date: 2023-07-19)

Primary citation

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.
Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.
Life Sci Alliance, 6:-, 2023

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.

PubMed: 37402591
DOI: 10.26508/lsa.202201796

Experimental method

ELECTRON MICROSCOPY (2.57 Å)