OmniVira

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.
PMID28393837 DOI10.1038/ncomms15092 Year2017 Journal Nature communications Nat Commun Languageeng Statusepublish

Abstract

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.

Supporting text Virus Host Location
Cryoelectron Microscopy 37 Antibodies, Neutralizing 80 Antiviral Agents 21 Glycoproteins 23 Glycosylation 22 Membrane Fusion 11 Middle East Respiratory Syndrome Coronavirus 68 Models, Molecular 99 Protein Binding 193 Protein Domains 45 Protein Multimerization 4 Receptors, Virus 204 Severe acute respiratory syndrome-related coronavirus 78 Spike Glycoprotein, Coronavirus 274 spike glycoprotein, SARS-CoV 16

Evidence records

2 total
Functional Mechanism
2 records · 1 evidence types
Evidence type Receptor Usage
2 records
OVE2587 Receptor Usage
Key finding

Cryo‑EM structural analysis showed that the receptor‑binding domain of the SARS‑CoV spike protein can switch between buried and exposed states, revealing conformational flexibility relevant to receptor recognition.

Virus
Severe Acute Respiratory Syndrome Coronavirus
Host
Not specified
Location
Not specified
Supporting text

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. 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
Receptors
receptor (unspecified)
OVE2588 Receptor Usage
Key finding

Cryo‑EM structural analysis showed that the receptor‑binding domain of the MERS‑CoV spike protein alternates between buried and exposed conformations, consistent with a mechanism enabling receptor interaction.

Virus
Middle East Respiratory Syndrome Coronavirus
Host
Not specified
Location
Not specified
Supporting text

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. 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
Receptors
receptor (unspecified)