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Literature detail

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.

Qihui Wang1,2,3 Yanfang Zhang4,5,6 Lili Wu1,7 Sheng Niu4,8 Chunli Song1,9 Zengyuan Zhang4,7 Guangwen Lu10 Chengpeng Qiao11 Yu Hu4,12 Kwok-Yung Yuen13,14 Qisheng Wang15 Huan Zhou15 Jinghua Yan1,2,4,16,17 Jianxun Qi4,18
Affiliations 18 institutions
  1. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  2. Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China
  3. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  4. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  5. University of the Chinese Academy of Sciences, Beijing 100049, China
  6. Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin 300308, China.
  7. University of the Chinese Academy of Sciences, Beijing 100049, China.
  8. College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China.
  9. Institute of Physical Science and Information, Anhui University, Hefei 230039, China.
  10. West China Hospital Emergency Department (WCHED), State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
  11. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  12. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
  13. State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China
  14. Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.
  15. Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.
  16. Institute of Physical Science and Information, Anhui University, Hefei 230039, China
  17. College of Life Science, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
  18. Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
PMID 32275855 2020 Cell eng ppublish
PubMed DOI Browse context

Article

Publication summary

The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.

ACE2 crystal structure CTD immunogenicity receptor receptor binding domain SARS-CoV-2 Virus Internalization Amino Acid Sequence Angiotensin-Converting Enzyme 2 Betacoronavirus Epitopes Humans Models, Molecular Peptidyl-Dipeptidase A Phylogeny Protein Domains SARS-CoV-2

Structured evidence records

Evidence records

2 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

Residue substitutions in the SARS-CoV-2 spike receptor-binding domain strengthen binding affinity to human ACE2 relative to SARS-CoV, indicating molecular adaptation in receptor binding.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

Atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD.

Genes or proteins
spike protein; CTD; RBD
Receptors
ACE2
Mechanism types
receptor_binding
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

SARS-CoV-2 binds human ACE2 to mediate viral entry, with structural analysis showing high-affinity receptor interaction compared to SARS-CoV.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 spike protein in complex with human ACE2, which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV.

Method
crystal structure analysis; structural study
Receptors
ACE2