title: Putative Receptor Binding Domain of Bat-Derived Coronavirus HKU9 Spike Protein: Evolution of Betacoronavirus Receptor Binding Motifs.
abstract: The suggested bat origin for Middle East respiratory syndrome coronavirus (MERS-CoV) has revitalized the studies of other bat-derived coronaviruses with respect to interspecies transmission potential. Bat coronavirus (BatCoV) HKU9 is an important betacoronavirus (betaCoV) that is phylogenetically affiliated with the same genus as MERS-CoV. The bat surveillance data indicated that BatCoV HKU9 has been widely spreading and circulating in bats. This highlights the necessity of characterizing the virus for its potential to cross species barriers. The receptor binding domain (RBD) of the coronavirus spike (S) protein recognizes host receptors to mediate virus entry and is therefore a key factor determining the viral tropism and transmission capacity. In this study, the putative S RBD of BatCoV HKU9 (HKU9-RBD), which is homologous to other betaCoV RBDs that have been structurally and functionally defined, was characterized via a series of biophysical and crystallographic methods. By using surface plasmon resonance, we demonstrated that HKU9-RBD binds to neither SARS-CoV receptor ACE2 nor MERS-CoV receptor CD26. We further determined the atomic structure of HKU9-RBD, which as expected is composed of a core and an external subdomain. The core subdomain fold resembles those of other betaCoV RBDs, whereas the external subdomain is structurally unique with a single helix, explaining the inability of HKU9-RBD to react with either ACE2 or CD26. Via comparison of the available RBD structures, we further proposed a homologous intersubdomain binding mode in betaCoV RBDs that anchors the external subdomain to the core subdomain. The revealed RBD features would shed light on the evolution route of betaCoV.
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC) , Beijing 102206, China.
authors.forename: Canping
authors.initials: C
authors.lastname: Huang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.affiliation: 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.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Lu
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Life Sciences, University of Science and Technology of China , Hefei, Anhui Province 230026, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC) , Beijing 102206, 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 Province 230026, China.|Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences , Tianjin 300308, China.|Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000818:Animals; D001665:Binding Sites; D002685:Chiroptera; D017934:Coronavirus / Q000737:chemistry / Q000145:classification; D018360:Crystallography, X-Ray; D010802:Phylogeny; D011487:Protein Conformation; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D064370:Spike Glycoprotein, Coronavirus