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Title | Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes. |
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Journal, issue, pages | Life Sci Alliance, Vol. 6, Issue 9, Year 2023 |
Publish date | Jul 4, 2023 |
Authors | Xixi Zhang / Zimu Li / Yanjun Zhang / Yutong Liu / Jingjing Wang / Banghui Liu / Qiuluan Chen / Qian Wang / Lutang Fu / Peiyi Wang / Xiaolin Zhong / Liang Jin / Qihong Yan / Ling Chen / Jun He / Jincun Zhao / Xiaoli Xiong / |
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 ...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. |
External links | Life Sci Alliance / PubMed:37402591 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.57 - 4.05 Å |
Structure data | EMDB-34417, PDB-8h0x: EMDB-34418, PDB-8h0y: EMDB-34419, PDB-8h0z: EMDB-34420, PDB-8h10: EMDB-34421, PDB-8h11: EMDB-34422, PDB-8h12: EMDB-34423, PDB-8h13: EMDB-34424, PDB-8h14: EMDB-34425, PDB-8h15: EMDB-34426, PDB-8h16: |
Chemicals | ChemComp-EIC: ChemComp-NAG: ChemComp-BLA: |
Source |
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Keywords | VIRAL PROTEIN / PROTEIN ENGINEERING / SPIKE PROTEIN / SARS-COV-1 / SARS-COV |