The Structure of theCyprinid herpesvirus 3ORF112-Zα·Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response

• Main Author: Kuś, Krzysztof
• Publication Date: 2015
• Other Authors: Rakus, Krzysztof, Boutier, Maxime, Tsigkri, Theokliti, Gabriel, Luisa, Vanderplasschen, Alain, Athanasiadis, Alekos
• Format: Article
• Language: eng
• Source: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Download full: http://hdl.handle.net/10400.7/611
• topic: Amino Acid Sequence; Animals; Binding Sites; Carps; Conserved Sequence; DNA, Z-Form; DNA-Activated Protein Kinase; Fish Diseases; Interferons; Models, Molecular; Nucleic Acid Conformation; Poxviridae; Protein Binding; Protein Structure, Tertiary; RNA Viruses; RNA, Double-Stranded; Viral Proteins

In vertebrate species, the innate immune system down-regulates protein translation in response to viral infection through the action of the double-stranded RNA (dsRNA)-activated protein kinase (PKR). In some teleost species another protein kinase, Z-DNA-dependent protein kinase (PKZ), plays a similar role but instead of dsRNA binding domains, PKZ has Zα domains. These domains recognize the left-handed conformer of dsDNA and dsRNA known as Z-DNA/Z-RNA. Cyprinid herpesvirus 3 infects common and koi carp, which have PKZ, and encodes the ORF112 protein that itself bears a Zα domain, a putative competitive inhibitor of PKZ. Here we present the crystal structure of ORF112-Zα in complex with an 18-bp CpG DNA repeat, at 1.5 Å. We demonstrate that the bound DNA is in the left-handed conformation and identify key interactions for the specificity of ORF112. Localization of ORF112 protein in stress granules induced in Cyprinid herpesvirus 3-infected fish cells suggests a functional behavior similar to that of Zα domains of the interferon-regulated, nucleic acid surveillance proteins ADAR1 and DAI.