Sequence discrimination of the Zα domain of human ADAR1 during B–Z transition of DNA duplexes

The Zα domain of human ADAR1 (ZαADAR1) preferentially binds Z-DNA rather than B-DNA with high binding affinity. ZαADAR1 binds to the Z-conformation of both non-CG-repeat DNA duplexes and a d(CGCGCG)2 duplex similarly. We performed NMR experiments on complexes between the ZαADAR1 and non-CG-repeat DNA duplexes, d(CACGTG)2 or d(CGTACG)2, with a variety of protein-DNA molar ratios. Comparison of these results with those from the analysis of d(CGCGCG)2 in the previous study suggests that ZαADAR1 exhibits the sequence preference of d(CGCGCG)2 ≫ d(CACGTG)2 > d(CGTACG)2 through multiple sequence discrimination steps during the B–Z transition.