Crystal structure of a poxvirus-like zalpha domain from cyprinid herpesvirus 3

Zalpha domains are a subfamily of the winged helix-turn-helix domains sharing the unique ability to recognize CpG repeats in the left-handed Z-DNA conformation. In vertebrates, domains of this family are found exclusively in proteins that detect foreign nucleic acids and activate components of the antiviral interferon response. Moreover, poxviruses encode the Zalpha domain-containing protein E3L, a well-studied and potent inhibitor of interferon response. Here we describe a herpesvirus Zalpha-domain-containing protein (ORF112) from cyprinid herpesvirus 3. We demonstrate that ORF112 also binds CpG repeats in the left-handed conformation, and moreover, its structure at 1.75 Å reveals the Zalpha fold found in ADAR1, DAI, PKZ, and E3L. Unlike other Zalpha domains, however, ORF112 forms a dimer through a unique domain-swapping mechanism. Thus, ORF112 may be considered a new member of the Z-domain family having DNA binding properties similar to those of the poxvirus E3L inhibitor of interferon response.

Keywords

Chromatography, Gel Cloning, Molecular CpG Islands Crystallography DNA Viruses Dimerization Open Reading Frames Protein Folding Viral Proteins Models, Molecular Protein Conformation

URI

http://hdl.handle.net/10400.7/484

Citation

Crystal Structure of a Poxvirus-Like Zalpha Domain from Cyprinid Herpesvirus 3 Ana Rita Tomé, Krzysztof Kuś, Silvia Correia, Lara Martins Paulo, Sónia Zacarias, Matteo de Rosa, Delio Figueiredo, R. Michael E. Parkhouse, and Alekos Athanasiadis J. Virol. April 2013 87:7 3998-4004; Accepted manuscript posted online 30 January 2013, doi:10.1128/JVI.03116-12