%0 Journal Article %A Sui, Baokun %A Huang, Junhua %A Jha, Babal K. %A Yin, Ping %A Zhou, Ming %A Fu, Zhen F. %A Silverman, Robert H. %A Weiss, Susan R. %A Peng, Guiqing %A Zhao, Ling %T Crystal structure of the mouse hepatitis virus ns2 phosphodiesterase domain that antagonizes RNase L activation %D 2016 %J Journal of General Virology, %V 97 %N 4 %P 880-886 %@ 1465-2099 %R https://doi.org/10.1099/jgv.0.000395 %I Microbiology Society, %X 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000395