1887

Abstract

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 (AKAP7) 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.

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2016-04-01
2021-10-27
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