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

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 (Zα and Zβ) at the NH 2 terminus. The hZβ 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 hZβ DAI with DNA duplex, d(CGCGCG) 2, at a variety of protein-to-DNA molar ratios. The results suggest that hZβ DAI binds to Z-DNA via an active-di B–Z transition mechanism, where two hZβ DAI proteins bind to B-DNA to form the hZβ 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.