Crystal structure of the C-terminal 2',5'-phosphodiesterase domain of group A rotavirus protein VP3

Proteins. 2015 May;83(5):997-1002. doi: 10.1002/prot.24794. Epub 2015 Mar 25.


In response to viral infections, the mammalian innate immune system induces the production of the second messenger 2'-5' oligoadenylate (2-5A) to activate latent ribonuclease L (RNase L) that restricts viral replication and promotes apoptosis. A subset of rotaviruses and coronaviruses encode 2',5'-phosphodiesterase enzymes that hydrolyze 2-5A, thereby inhibiting RNase L activation. We report the crystal structure of the 2',5'-phosphodiesterase domain of group A rotavirus protein VP3 at 1.39 Å resolution. The structure exhibits a 2H phosphoesterase fold and reveals conserved active site residues, providing insights into the mechanism of 2-5A degradation in viral evasion of host innate immunity.

Keywords: 2-5A; 2H phosphoesterase; RNase L; immune evasion; innate immunity; oligoadenylate synthase; phosphodiesterase; rotavirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid Proteins / chemistry*
  • Catalytic Domain
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Models, Molecular
  • Phosphoric Diester Hydrolases / chemistry*
  • Protein Structure, Secondary
  • Rotavirus / enzymology*


  • Capsid Proteins
  • VP3 protein, Rotavirus
  • Phosphoric Diester Hydrolases

Associated data

  • PDB/5AF2