Structural highlights
FunctionPublication Abstract from PubMedIn vertebrate species the innate immune system down-regulates protein translation in response to viral infection through the action of the dsRNA-activated protein kinase (PKR). In some teleost species another 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 (CyHV-3) infects common and koi carp, that 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 CyHV-3 infected fish cells suggests a functional behaviour similar to that of Zalpha domains of the interferon-regulated, nucleic acid surveillance proteins ADAR1 and DAI. 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.,Kus K, Rakus K, Boutier M, Tsigkri T, Gabriel L, Vanderplasschen A, Athanasiadis A J Biol Chem. 2015 Nov 11. pii: jbc.M115.679407. PMID:26559969[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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