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Literature detail

Structure of the S1 subunit C-terminal domain from bat-derived coronavirus HKU5 spike protein.

Xue Han1,2 Jianxun Qi3 Hao Song1,4 Qihui Wang5,6 Yanfang Zhang1,2 Ying Wu7,8 Guangwen Lu9 Kwok-Yung Yuen10,11,12 Yi Shi1,13,7,14 George F Gao1,13,15,7,16,17,18
Affiliations 18 institutions
  1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  2. University of Chinese Academy of Sciences, Beijing 100049, China.
  3. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  4. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
  5. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  6. Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
  7. Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China
  8. School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
  9. 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.
  10. State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam 999077, Hong Kong Special Administration Region
  11. Department of Microbiology, The University of Hong Kong, Pokfulam 999077, Hong Kong Special Administration Region
  12. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
  13. University of Chinese Academy of Sciences, Beijing 100049, China
  14. Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China. Electronic address: [email protected].
  15. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China
  16. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China
  17. Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China
  18. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: [email protected].
PMID 28432925 2017 Virology eng ppublish
PubMed DOI Browse context

Article

Publication summary

Accumulating evidence indicates that MERS-CoV originated from bat coronaviruses (BatCoVs). Previously, we demonstrated that both MERS-CoV and BatCoV HKU4 use CD26 as a receptor, but how the BatCoVs evolved to bind CD26 is an intriguing question. Here, we solved the crystal structure of the S1 subunit C-terminal domain of HKU5 (HKU5-CTD), another BatCoV that is phylogenetically related to MERS-CoV but cannot bind to CD26. We observed that the conserved core subdomain and those of other betacoronaviruses (betaCoVs) have a similar topology of the external subdomain, indicating the same ancestor of lineage C betaCoVs. However, two deletions in two respective loops located in HKU5-CTD result in conformational variations in CD26-binding interface and are responsible for the non-binding of HKU5-CTD to CD26. Combined with sequence variation in the HKU5-CTD receptor binding interface, we propose the necessity for surveilling the mutation in BatCoV HKU5 spike protein in case of bat-to-human interspecies transmission.

BatCoV HKU5 Crystal structure CTD Evolution MERS-CoV Amino Acid Sequence Animals Chiroptera Coronavirus Coronavirus Infections Dipeptidyl Peptidase 4 Molecular Sequence Data Protein Conformation Protein Domains Receptors, Virus Sequence Alignment Spike Glycoprotein, Coronavirus

Structured evidence records

Evidence records

3 total
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.75
Key finding

Structural and sequence comparison of the HKU5 spike C-terminal domain shows phylogenetic relatedness to MERS-CoV and lineage C betacoronaviruses, indicating shared ancestry and evolutionary divergence affecting CD26 binding.

Virus
BatCoV-HKU5
Host
Chiroptera
Location
Not specified
Supporting text

We solved the crystal structure of the S1 subunit C-terminal domain of HKU5 (HKU5-CTD), another BatCoV that is phylogenetically related to MERS-CoV. We observed that the conserved core subdomain and those of other betacoronaviruses have similar topology, indicating the same ancestor of lineage C betaCoVs. Combined with sequence variation in the HKU5-CTD receptor binding interface, we propose the necessity for surveilling the mutation in BatCoV HKU5 spike protein.

Genes or proteins
spike protein; S1 subunit C-terminal domain; HKU5-CTD
Analysis methods
structural analysis; sequence comparison; phylogenetic analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

Loop deletions in the HKU5 spike C-terminal domain alter the CD26-binding interface, preventing receptor binding and indicating molecular adaptation differences within lineage C betacoronaviruses.

Virus
BatCoV-HKU5
Host
Not specified
Location
Not specified
Supporting text

Two deletions in two respective loops located in HKU5-CTD result in conformational variations in CD26-binding interface and are responsible for the non-binding of HKU5-CTD to CD26.

Genes or proteins
spike protein; S1 subunit C-terminal domain
Receptors
CD26
Mechanism types
receptor_binding; cell_entry
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.95
Key finding

BatCoV HKU5 spike protein lacks the ability to bind the CD26 receptor due to deletions in the C-terminal domain that disrupt the receptor-binding interface.

Virus
BatCoV-HKU5
Host
Chiroptera
Location
Not specified
Supporting text

We solved the crystal structure of the S1 subunit C-terminal domain of HKU5 (HKU5-CTD)... another BatCoV that is phylogenetically related to MERS-CoV but cannot bind to CD26. Two deletions in HKU5-CTD result in conformational variations in the CD26-binding interface and are responsible for the non-binding of HKU5-CTD to CD26.

Method
crystal structure analysis
Receptors
CD26