Key result
The crystal structure of the mouse hepatitis virus ns2 phosphodiesterase domain reveals a conserved catalytic groove with HxT/Sx motifs that provides the structural basis for 2-5A binding and cleavage.
The crystal structure of the MHV ns2 PDE domain reveals the structural basis for its 2',5'-oligoadenylate cleavage activity, providing insights into how coronaviruses evade host innate immunity.
Structural basis for MHV ns2 PDE activity extends coronavirus immune evasion models; leaves open antiviral targeting in humans.
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(CD)) 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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Sui et al. (2016) studied Mouse hepatitis virus (MHV) infection. MHV ns2 PDE domain was evaluated on Crystal structure determination and 2',5'-PDE activity. The crystal structure of the mouse hepatitis virus ns2 phosphodiesterase domain reveals a conserved catalytic groove with HxT/Sx motifs that provides the structural basis for 2-5A binding and cleavage.
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