SNAP output for PDB entry 4wcg [SNAP web server]

PDB-id

4wcg; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein

Method

X-ray (1.5 Å)

Summary

The binding mode of cyprinid herpesvirus3 orf112-zalpha to z-DNA

Reference

Kus K, Rakus K, Boutier M, Tsigkri T, Gabriel L, Vanderplasschen A, Athanasiadis A (2015): "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. doi: 10.1074/jbc.M115.679407.

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.