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Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains.

Yuan Yuan1,2 Duanfang Cao3 Yanfang Zhang2,4 Jun Ma3 Jianxun Qi2 Qihui Wang5 Guangwen Lu6 Ying Wu7 Jinghua Yan5,8,9,10 Yi Shi2,8,9,10 Xinzheng Zhang3,11 George F Gao1,2,4,8,9,10,12
Affiliations 12 institutions
  1. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
  2. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  3. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  4. Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin 300308, China.
  5. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  6. West China Hospital Emergency Department (WCHED), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
  7. School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
  8. Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
  9. Center for Influenza Research and Early-warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China.
  10. Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
  11. Center for Biological Imaging, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  12. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
PMID 28393837 2017 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.

Cryoelectron Microscopy Antibodies, Neutralizing Antiviral Agents Glycoproteins Glycosylation Membrane Fusion Middle East Respiratory Syndrome Coronavirus Models, Molecular Protein Binding Protein Domains Protein Multimerization Receptors, Virus Severe acute respiratory syndrome-related coronavirus Spike Glycoprotein, Coronavirus spike glycoprotein, SARS-CoV

Structured evidence records

Evidence records

2 total
Receptor Usage 2 records
Receptor Usage Extraction confidence 0.95
Key finding

MERS-CoV spike receptor binding domain exhibits structural flexibility with conformations that modulate receptor accessibility.

Virus
MERS-CoV
Host
Not specified
Location
Not specified
Supporting text

We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor.

Method
cryo-electron microscopy; structural analysis
Receptors
receptor
Receptor Usage Extraction confidence 0.95
Key finding

SARS-CoV spike receptor binding domain shows conformational states that control receptor exposure for host cell entry.

Virus
SARS-CoV
Host
Not specified
Location
Not specified
Supporting text

We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor.

Method
cryo-electron microscopy; structural analysis
Receptors
receptor