posters 5th Asia-Pacific NMR Symposium 2013

NMR Spectroscopic Elucidation of the A-to-Z Helical Transition of RNA Duplexes Induced by Z-DNA Binding Proteins (#158)

Moon-Young Kwon 1 , Ju-Yong Lee , Ae-Ree Lee , Joon-Hwa Lee , Hee-Eun Kim
  1. Gyeongsang National University, Jinju, Gyeongnam, South Korea

Double-stranded RNA deaminase I (ADAR1) deaminates adenine in pre-mRNA to yield inosine (I), which codes as a guanine residue in mRNA. These A-to-I conversions can lead to functional changes in the resulting proteins. At its NH2-terminus, ADAR1 has two left-handed Z-DNA binding domains and preferentially binds Z-DNA, rather than B-DNA, with high binding affinity. The main difference between DNA and RNA is the presence of the ribose 2’-OH groups; however, this difference makes the two macromolecules very different with regard to their biochemical behavior as well as the structures they adopt as double helices. Both B-DNA and A-RNA can undergo a transition to left-handed double-helical structures, referred to as Z-DNA and Z-RNA. The crystal structural study of the Z-DNA binding domain of ADAR1 complexed to a dUr(CG)3 duplex RNA found that the Z-RNA helix is associated with a unique solvent pattern that distinguishes it from the otherwise similar conformation of Z-DNA. In order to characterize the molecular recognition of Z-RNA by ADAR1, we performed NMR experiments with complexes of ADAR1 bound to r(CGCGCG)2 and these results were compared with those of Z-DNA, d(CGCGCG)2, induced by ADAR1 previously reported. This study provides insight into the interaction of Z-DNA binding domain with Z-RNA which demonstrates how the ADAR1 isoform could be targeted toward selected dsRNAs containing purine-pyrimidine repeats, possibly of viral origin.