2. Academic Validation
  3. Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes

Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes

  • Nat Commun. 2021 Jan 8;12(1):141. doi: 10.1038/s41467-020-20401-y.
Xiyong Song 1 2 3,  Yuejun Shi 1 4,  Wei Ding 5,  Tongxin Niu 6,  Limeng Sun 1 4,  Yubei Tan 1 4,  Yong Chen 2 3,  Jiale Shi 1 4,  Qiqi Xiong 1 4,  Xiaojun Huang 6,  Shaobo Xiao 1 4,  Yanping Zhu 2,  Chongyun Cheng 2,  Zhen F Fu 1 4 7,  Zhi-Jie Liu 8 9,  Guiqing Peng 10 11
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
  • 2 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 3 University of Chinese Academy of Sciences, Beijing, China.
  • 4 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China.
  • 5 CAS Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, P.O.Box 603, Beijing, China.
  • 6 Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 7 Departments of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • 8 Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China. liuzhj@shanghaitech.edu.cn.
  • 9 iHuman Institute, ShanghaiTech University, Shanghai, China. liuzhj@shanghaitech.edu.cn.
  • 10 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. penggq@mail.hzau.edu.cn.
  • 11 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China. penggq@mail.hzau.edu.cn.
PMID: 33420048 DOI: 10.1038/s41467-020-20401-y
Abstract

Coronaviruses spike (S) glycoproteins mediate viral entry into host cells by binding to host receptors. However, how the S1 subunit undergoes conformational changes for receptor recognition has not been elucidated in Alphacoronavirus. Here, we report the cryo-EM structures of the HCoV-229E S trimer in prefusion state with two conformations. The activated conformation may pose the potential exposure of the S1-RBDs by decreasing of the interaction area between the S1-RBDs and the surrounding S1-NTDs and S1-RBDs compared to the closed conformation. Furthermore, structural comparison of our structures with the previously reported HCoV-229E S structure showed that the S trimers trended to open the S2 subunit from the closed conformation to open conformation, which could promote the transition from pre- to postfusion. Our results provide insights into the mechanisms involved in S glycoprotein-mediated Alphacoronavirus entry and have implications for vaccine and therapeutic antibody design.

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