4Z5V

Crystal Structure of MHV ns2 PDE Domain

Summary for 4Z5V

• Entry DOI: 10.2210/pdb4z5v/pdb
• Descriptor: Non-structural protein 2a (1 entity in total)
• Functional Keywords: murine hepatitis virus, ns2 protein, phosphodiesterase, viral protein
• Biological source: Murine coronavirus (strain A59) (MHV-A59)
• Cellular location: Host cytoplasm : P19738
• Total number of polymer chains: 2
• Total formula weight: 48279.70

Authors

Sui, B.K.,Huang, J.H.,Peng, G.Q.,Zhao, L. (deposition date: 2015-04-03, release date: 2016-02-10, Last modification date: 2024-11-20)

Primary citation

Sui, B.K.,Huang, J.H.,Jha, B.K.,Yin, P.,Zhou, M.,Fu, Z.F.,Silverman, R.H.,Weiss, S.R.,Peng, G.Q.,Zhao, L.
Crystal structure of the mouse hepatitis virus ns2 phosphodiesterase domain that antagonizes RNase L activation
J.Gen.Virol., 97:880-886, 2016

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.

PubMed: 26757803
DOI: 10.1099/jgv.0.000395

Experimental method

X-RAY DIFFRACTION (3.049 Å)