Macro domain from middle east respiratory syndrome coronavirus (MERS-CoV) is an efficient ADP-ribose binding module: Crystal structure and biochemical studies
Journal
Journal of Biological Chemistry
Journal Volume
291
Journal Issue
10
Start Page
4894
End Page
4902
ISSN
00219258
Date Issued
2016-03-04
Author(s)
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.
SDGs
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Type
journal article