title: Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4.
abstract: The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Nianshuang
authors.initials: N
authors.lastname: Wang
authors.forename: Xuanling
authors.initials: X
authors.lastname: Shi
authors.forename: Liwei
authors.initials: L
authors.lastname: Jiang
authors.forename: Senyan
authors.initials: S
authors.lastname: Zhang
authors.forename: Dongli
authors.initials: D
authors.lastname: Wang
authors.forename: Pei
authors.initials: P
authors.lastname: Tong
authors.forename: Dongxing
authors.initials: D
authors.lastname: Guo
authors.forename: Lili
authors.initials: L
authors.lastname: Fu
authors.forename: Ye
authors.initials: Y
authors.lastname: Cui
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Arledge
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D017934:Coronavirus / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism; D061987:Sf9 Cells; D018411:Spodoptera; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D014764:Viral Proteins; D018819:Dipeptidyl Peptidase 4