The Structure of the Cyprinid herpesvirus 3 ORF112-Zalpha.Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response.
Amino Acid Sequence; Animals; Binding Sites; Carps; Conserved Sequence; DNA, Z-Form/chemistry/genetics/metabolism; DNA-Activated Protein Kinase/chemistry/genetics/metabolism; Fish Diseases/virology; Interferons/genetics/metabolism; Models, Molecular; Nucleic Acid Conformation; Poxviridae/chemistry/enzymology/genetics; Protein Binding; Protein Structure, Tertiary; RNA Viruses/chemistry/enzymology/genetics; RNA, Double-Stranded/chemistry/genetics/metabolism; Viral Proteins/chemistry/genetics/metabolism; DNA viruses; X-ray crystallography; Zalpha domain; interferon; protein-nucleic acid interaction; stress granule
Abstract :
[en] 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 Zalpha 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 Zalpha domain, a putative competitive inhibitor of PKZ. Here we present the crystal structure of ORF112-Zalpha in complex with an 18-bp CpG DNA repeat, at 1.5 A. 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 Zalpha domains of the interferon-regulated, nucleic acid surveillance proteins ADAR1 and DAI.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kus, Krzysztof
Rakus, Krzysztof
Boutier, Maxime ; Université de Liège > Immunologie et vaccinologie
The Structure of the Cyprinid herpesvirus 3 ORF112-Zalpha.Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response.
Publication date :
2015
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, United States - Maryland
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