Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES

J Biol Chem. 2016 Mar 4;291(10):4894-902. doi: 10.1074/jbc.M115.700542. Epub 2016 Jan 5.

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.

Keywords: ADP-ribosylation; RNA virus; biophysics; crystal structure; viral protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Middle East Respiratory Syndrome Coronavirus / chemistry*
  • Middle East Respiratory Syndrome Coronavirus / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism

Substances

  • Viral Proteins
  • Adenosine Diphosphate Ribose

Associated data

  • PDB/2FAV
  • PDB/2VRI
  • PDB/3EWP
  • PDB/3EWR
  • PDB/3JZT
  • PDB/5DUS