title: Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES.
abstract: The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) encodes the conserved macro domain within non-structural protein 3. However, the precise biochemical function and structure of the macro domain is unclear. Using differential scanning fluorimetry and isothermal titration calorimetry, we characterized the MERS-CoV macro domain as a more efficient adenosine diphosphate (ADP)-ribose binding module than macro domains from other CoVs. Furthermore, the crystal structure of the MERS-CoV macro domain was determined at 1.43-Å resolution in complex with ADP-ribose. Comparison of macro domains from MERS-CoV and other human CoVs revealed structural differences in the α1 helix alters how the conserved Asp-20 interacts with ADP-ribose and may explain the efficient binding of the MERS-CoV macro domain to ADP-ribose. This study provides structural and biophysical bases to further evaluate the role of the MERS-CoV macro domain in the host response via ADP-ribose binding but also as a potential target for drug design.
authors.affiliation: From the Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617.
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Cho
authors.affiliation: From the Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Lin
authors.affiliation: the Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, and the Center for Systems Biology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Chuang
authors.affiliation: From the Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, the Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, and the Center for Systems Biology, National Taiwan University, Taipei 10617, Taiwan andyhsu@ntu.edu.tw.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hsu
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D065207:Middle East Respiratory Syndrome Coronavirus / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D000246:Adenosine Diphosphate Ribose
keywords: ADP-ribosylation; RNA virus; biophysics; crystal structure; viral protein