NMR dynamics study of the Z-DNA binding domain of human ADAR1 bound to various DNA duplexes

The Z-DNA binding domain of human ADAR1 (ZαADAR1) preferentially binds Z-DNA rather than B-DNA with high binding affinity. Here, we have carried out chemical shift perturbation and backbone dynamics studies of ZαADAR1 in the free form and in complex with three DNA duplexes, d(CGCGCG)2, d(CACGTG)2, and d(CGTACG)2. This study reveals that ZαADAR1 initially binds to d(CGCGCG)2 through the distinct conformation, especially in the unusually flexible β1–loop–α2 region, from the d(CGCGCG)2–(ZαADAR1)2 complex. This study also suggests that ZαADAR1 exhibits a distinct conformational change during the B–Z transition of non-CG-repeat DNA duplexes with low binding affinities compared to the CG-repeat DNA duplex.

► ZαADAR1 initially binds to CG-repeat DNA through a distinct conformation.
► ZαADAR1 exhibits a distinct conformational change during the B–Z transition of non-CG-repeat DNA.
► ZαADAR1 binds to non-CG-repeat DNA with a low binding affinity compared to the CG-repeat DNA.