Crystal structure of the mouse hepatitis virus ns2 phosphodiesterase domain that antagonizes RNase L activation.

Research paper by Baokun B Sui, Junhua J Huang, Babal K BK Jha, Ping P Yin, Ming M Zhou, Zhen F ZF Fu, Robert H RH Silverman, Susan R SR Weiss, Guiqing G Peng, Ling L Zhao

Indexed on: 14 Jan '16Published on: 14 Jan '16Published in: The Journal of general virology


Prior studies have demonstrated that the mouse hepatitis virus (MHV) A59 strain ns2 protein is a member of the 2H phosphoesterase family and exhibits 2',5'-phosphodiesterase (PDE) activity. During the IFN antiviral response, ns2 cleaves 2',5'-oligoadenylate (2-5A), a key mediator of RNase L activation, thereby subverting the activation of RNase L and evading host innate immunity. However, the mechanism of 2-5A cleavage by ns2 remains unclear. Here, we present the crystal structure of the MHV ns2 PDE domain and demonstrate a PDE fold similar to that of the cellular protein, a kinase anchoring protein 7 central domain (AKAP7CD) and rotavirus VP3 carboxy-terminal domain. The structure displays a pair of strictly conserved HxT/Sx motifs and forms a deep, positively charged catalytic groove with β-sheets and an arginine-containing loop. These findings provide insight into the structural basis for 2-5A binding of MHV ns2.