4Z5V

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

(2016) J Gen Virol 97: 880-886

• PubMed: 26757803 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1099/jgv.0.000395
• Primary Citation of Related Structures:  
  4Z5V


• PubMed 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(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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Organizational Affiliation: 

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PRChina.