title: The Structure of the Cyprinid herpesvirus 3 ORF112-Zα·Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response.
abstract: 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.
authors.affiliation: From the Instituto Gulbenkian de Ciência, 2781-156, Oeiras, Portugal and.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kuś
authors.affiliation: the Immunology-Vaccinology Laboratory, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Rakus
authors.affiliation: the Immunology-Vaccinology Laboratory, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.
authors.forename: Maxime
authors.initials: M
authors.lastname: Boutier
authors.affiliation: From the Instituto Gulbenkian de Ciência, 2781-156, Oeiras, Portugal and.
authors.forename: Theokliti
authors.initials: T
authors.lastname: Tsigkri
authors.affiliation: From the Instituto Gulbenkian de Ciência, 2781-156, Oeiras, Portugal and.
authors.forename: Luisa
authors.initials: L
authors.lastname: Gabriel
authors.affiliation: the Immunology-Vaccinology Laboratory, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Vanderplasschen
authors.affiliation: From the Instituto Gulbenkian de Ciência, 2781-156, Oeiras, Portugal and alekos@igc.gulbenkian.pt.
authors.forename: Alekos
authors.initials: A
authors.lastname: Athanasiadis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002347:Carps; D017124:Conserved Sequence; D043542:DNA, Z-Form / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051747:DNA-Activated Protein Kinase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005393:Fish Diseases / Q000821:virology*; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011212:Poxviridae / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012328:RNA Viruses / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D043542:DNA, Z-Form; D012330:RNA, Double-Stranded; D014764:Viral Proteins; D007372:Interferons; D051747:DNA-Activated Protein Kinase
keywords: DNA viruses; X-ray crystallography; Zalpha domain; interferon; protein-nucleic acid interaction; stress granule