Crystal structures of two coronavirus ADP-ribose-1''-monophosphatases and their complexes with ADP-Ribose: a systematic structural analysis of the viral ADRP domain

J Virol. 2009 Jan;83(2):1083-92. doi: 10.1128/JVI.01862-08. Epub 2008 Nov 5.

Abstract

The coronaviruses are a large family of plus-strand RNA viruses that cause a wide variety of diseases both in humans and in other organisms. The coronaviruses are composed of three main lineages and have a complex organization of nonstructural proteins (nsp's). In the coronavirus, nsp3 resides a domain with the macroH2A-like fold and ADP-ribose-1"-monophosphatase (ADRP) activity, which is proposed to play a regulatory role in the replication process. However, the significance of this domain for the coronaviruses is still poorly understood due to the lack of structural information from different lineages. We have determined the crystal structures of two viral ADRP domains, from the group I human coronavirus 229E and the group III avian infectious bronchitis virus, as well as their respective complexes with ADP-ribose. The structures were individually solved to elucidate the structural similarities and differences of the ADRP domains among various coronavirus species. The active-site residues responsible for mediating ADRP activity were found to be highly conserved in terms of both sequence alignment and structural superposition, whereas the substrate binding pocket exhibited variations in structure but not in sequence. Together with data from a previous analysis of the ADRP domain from the group II severe acute respiratory syndrome coronavirus and from other related functional studies of ADRP domains, a systematic structural analysis of the coronavirus ADRP domains was realized for the first time to provide a structural basis for the function of this domain in the coronavirus replication process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / chemistry
  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Conserved Sequence
  • Coronavirus 229E, Human / chemistry*
  • Crystallography, X-Ray
  • Humans
  • Infectious bronchitis virus / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphoric Monoester Hydrolases / chemistry*
  • Protein Structure, Quaternary*
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Viral Nonstructural Proteins / chemistry*

Substances

  • Viral Nonstructural Proteins
  • Adenosine Diphosphate Ribose
  • Phosphoric Monoester Hydrolases