NMR spectroscopic elucidation of the B-Z transition of a DNA double helix induced by the Zα domain of human ADAR1
- NMR spectroscopic elucidation of the B-Z transition of a DNA double helix induced by the Zα domain of human ADAR1
- 강영민; 방종철; 이은해; 안희철; 서여진; 김경규; 김양균; 최병석; 이준화
- NMR; B-Z transition; Zα domain
- Issue Date
- Journal of the American Chemical Society
- VOL 131, NO 32, 11485-11491
- The human RNA editing enzyme ADAR1 (double-stranded RNA deaminase I) deaminates adenine in pre-mRNA to yield inosine, which codes as guanine. ADAR1 has two left-handed Z-DNA binding domains, Zα and Zβ, at its NH2-terminus and preferentially binds Z-DNA, rather than B-DNA, with high binding affinity. The cocrystal structure of ZαADAR1 complexed to Z-DNA showed that one monomeric ZαADAR1 domain binds to one strand of double-stranded DNA and a second ZαADAR1 monomer binds to the opposite strand with 2-fold symmetry with respect to DNA helical axis. It remains unclear how ZαADAR1 protein specifically recognizes Z-DNA sequence in a sea of B-DNA to produce the stable ZαADAR1−Z-DNA complex during the B−Z transition induced by ZαADAR1. In order to characterize the molecular recognition of Z-DNA by ZαADAR1, we performed circular dichroism (CD) and NMR experiments with complexes of ZαADAR1 bound to d(CGCGCG)2 (referred to as CG6) produced at a variety of protein-to-DNA molar ratios. From this study, we identified the intermediate states of the CG6−ZαADAR1 complex and calculated their relative populations as a function of the ZαADAR1 concentration. These findings support an active B−Z transition mechanism in which the ZαADAR1 protein first binds to B-DNA and then converts it to left-handed Z-DNA, a conformation that is then stabilized by the additional binding of a second ZαADAR1 molecule.
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