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ACS Chem Biol. 2019 Feb 15;14(2):245-255. doi: 10.1021/acschembio.8b00914. Epub 2019 Jan 11.

NMR Dynamics Study Reveals the Zα Domain of Human ADAR1 Associates with and Dissociates from Z-RNA More Slowly than Z-DNA.

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Department of Chemistry and RINS , Gyeongsang National University , Gyeongnam 52828 , South Korea.
Department of Chemistry , Korea Advanced Institute of Science and Technology , Daejeon 34141 , South Korea.
Department of Molecular Cell Biology , Sungkyunkwan University School of Medicine , Gyeonggi 16419 , South Korea.
Protein Structure Research Team , Korea Basic Science Institute , Chungbuk 28119 , South Korea.
Advanced Analysis Center , Korea Institute of Science and Technology , Seoul 02792 , South Korea.


Human RNA editing enzyme ADAR1 deaminates adenosine in pre-mRNA to yield inosine. The Zα domain of human ADAR1 (hZαADAR1) binds specifically to left-handed Z-RNA as well as Z-DNA and stabilizes the Z-conformation. To answer the question of how hZαADAR1 can induce both the B-Z transition of DNA and the A-Z transition of RNA, we investigated the structure and dynamics of hZαADAR1 in complex with 6-base-pair Z-DNA or Z-RNA. We performed chemical shift perturbation and relaxation dispersion experiments on hZαADAR1 upon binding to Z-DNA as well as Z-RNA. Our study demonstrates the unique dynamics of hZαADAR1 during the A-Z transition of RNA, in which the hZαADAR1 protein forms a thermodynamically stable complex with Z-RNA, similar to Z-DNA, but kinetically converts RNA to the Z-form more slowly than DNA. We also discovered some distinct structural features of hZαADAR1 in the Z-RNA binding conformation. Our results suggest that the A-Z transition of RNA facilitated by hZαADAR1 displays unique structural and dynamic features that may be involved in targeting ADAR1 for a role in recognition of RNA substrates.


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