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

Zhang, Xixi1,6; Li, Zimu1; Zhang, Yanjun2; Liu, Yutong1; Wang, Jingjing1; Liu, Banghui1; Chen, Qiuluan3,7; Wang, Qian2; Fu, Lutang4; Wang, Peiyi4; Zhong, Xiaolin3; Jin, Liang3; Yan, Qihong1,2; Chen, Ling1,2,5; He, Jun1; Zhao, Jincun2,5; Xiong, Xiaoli1

2023-09-01

10.26508/lsa.202201796

LIFE SCIENCE ALLIANCE   影响因子和分区

2575-1077

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.

SCI

英语

其他

Ramp;D Program of Guangzhou Laboratory["SRPG22-002","SRPG22-003"] ; Emergency Key Program of Guangzhou Laboratory[EKPG21-06] ; Natural Science Fund of Guangdong Province["2021A1515011289","2022A1515110495","2022A1515110211"] ; Guangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Diseases[2019B121205010]

Life Sciences & Biomedicine - Other Topics

Biology

WOS:001026116100001

LIFE SCIENCE ALLIANCE LLC

Web of Science

1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, CAS Key Lab Regenerat Biol,Guangdong Prov Key Lab, Guangzhou, Peoples R China
2.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, State Key Lab Resp Dis, Affiliated Hosp 1, Guangzhou, Peoples R China
3.Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou, Peoples R China
4.Southern Univ Sci & Technol, Cryoelectron Microscopy Ctr, Shenzhen, Peoples R China
5.Guangzhou Int Bio Isl, Guangzhou Lab, Guangzhou, Peoples R China
6.Zhejiang Univ, Liangzhu Lab, Hangzhou, Peoples R China
7.Yunzhou Biosci Guangzhou Co Ltd, Guangzhou, Peoples R China

Zhang, Xixi,Li, Zimu,Zhang, Yanjun,et al. Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes[J]. LIFE SCIENCE ALLIANCE,2023,6(9).

Zhang, Xixi.,Li, Zimu.,Zhang, Yanjun.,Liu, Yutong.,Wang, Jingjing.,...&Xiong, Xiaoli.(2023).Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.LIFE SCIENCE ALLIANCE,6(9).

Zhang, Xixi,et al."Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes".LIFE SCIENCE ALLIANCE 6.9(2023).