Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES* |
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| Authors: | Chao-Cheng Cho Meng-Hsuan Lin Chien-Ying Chuang Chun-Hua Hsu |
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| Institution: | 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 |
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| 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. |
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| Keywords: | ADP-ribosylation biophysics crystal structure RNA virus viral protein |
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