title: Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26.
abstract: The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans, representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV. CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV. The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 β-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein-protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among betacoronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Lu
authors.forename: Yawei
authors.initials: Y
authors.lastname: Hu
authors.forename: Qihui
authors.initials: Q
authors.lastname: Wang
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jinku
authors.initials: J
authors.lastname: Bao
authors.forename: Buchang
authors.initials: B
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D017124:Conserved Sequence / Q000235:genetics; D017934:Coronavirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D000085064:Receptors, Coronavirus; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D000085064:Receptors, Coronavirus; D011991:Receptors, Virus; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4