6LZG | pdb_00006lzg

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

(2020) Cell 181: 894-904.e9

• PubMed: 32275855 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1016/j.cell.2020.03.045
• Primary Citation of Related Structures:  
  6LZG


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 
• CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin 300308, China.
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China.
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Institute of Physical Science and Information, Anhui University, Hefei 230039, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
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.
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.
Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Institute of Physical Science and Information, Anhui University, Hefei 230039, China; College of Life Science, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: yanjh@im.ac.cn.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jxqi@im.ac.cn.
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