4WCG

The binding mode of Cyprinid Herpesvirus3 ORF112-Zalpha to Z-DNA

Summary for 4WCG

• Entry DOI: 10.2210/pdb4wcg/pdb
• Related: 4HOB
• Descriptor: ORF112, DNA (5'-D(P*CP*GP*CP*GP*CP*G)-3'), SULFATE ION, ... (4 entities in total)
• Functional Keywords: zalpha, z-dna, innate immunity, herpes virus, dna binding protein
• Biological source: Cyprinid herpesvirus 3; More
• Total number of polymer chains: 4
• Total formula weight: 33584.26

Authors

Kus, K.,Athanasiadis, A. (deposition date: 2014-09-04, release date: 2015-11-18, Last modification date: 2024-01-10)

Primary citation

Kus, K.,Rakus, K.,Boutier, M.,Tsigkri, T.,Gabriel, L.,Vanderplasschen, A.,Athanasiadis, A.
The Structure of the Cyprinid herpesvirus 3 ORF112-Z alpha Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response.
J.Biol.Chem., 290:30713-30725, 2015

PubMed 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.

PubMed: 26559969
DOI: 10.1074/jbc.M115.679407

Experimental method

X-RAY DIFFRACTION (1.5 Å)