The Z beta domain of human DAI binds to Z-DNA via a novel B-Z transition pathway

Abstract

The human DNA-dependent activator of IFN-regulatory factor (DAI) protein, which activates the innate immune response in response to DNA, contains two tandem Z-DNA binding domains (Z alpha and Z beta) at the NH2 terminus. The hZ beta(DAI) structure is similar to other Z-DNA binding proteins, although it demonstrates an unusual Z-DNA recognition. We performed NMR experiments on complexes of hZ beta(DAI) with DNA duplex, d(CGCGCG)(2), at a variety of protein-to-DNA molar ratios. The results suggest that hZ beta(DAI) binds to Z-DNA via an active-di B-Z transition mechanism, where two hZ beta(DAI) proteins bind to B-DNA to form the hZ beta(DAI)-B-DNA complex; the B-DNA is subsequently converted to left-handed Z-DNA. This novel mechanism of DNA binding and B-Z conversion is distinct from Z-DNA binding of the human ADAR1 protein. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.