STRUCT FUNCT OF Z DNA BINDING DOMAIN Z OF DSRNA ADENOSINE DEAMINASE TYPE I

RNA编辑通过位点选择性腺苷改变Pre-mRNA 去角化，这会导致密码子改变，从而导致 生产新的蛋白质。催化这个反应的一种酶， 双链RNA腺苷脱氨酶(ADARI)，含有两个N 末端Z-DNA结合基序，Z，，和4，其功能是AS 但还不清楚。在本研究中，多维核磁共振波谱被 用来证明Z“‘的拓扑是(X10 1(X2(X3 P2 03. 长程NOE表明P1和P3相互作用。 使用定点突变来鉴定0，03和 连接02和03的影响Z-DNA结合的环。也是 鉴定出了I I疏水残基，这些残基对 蛋白质稳定性。与已知结构的比较揭示了一些 Z，，和(oc+0)螺旋-Tm-螺旋蛋白之间的相似性，例如 组蛋白5与肝细胞核因子-3家族 翼状螺旋-螺旋-螺旋转录因子。总而言之， 结构和功能数据表明Z-DNA的识别 Z，，，涉及0螺旋和C-末端P-片中的残基。

RNA editing alters pre-mRNA through site-selective adenosine dearnination, which results in codon changes that lead to the production of novel proteins. An enzyme that catalyzes this reaction, double-stranded RNA adenosine deaminase (ADARI), contains two N terminal Z-DNA-binding motifs, Z,,, and 4, the function of which is as yet unknown. In this study, multidimensional NMR spectroscopy was used to show that the topology of Z"' is (X 10 1 (X2 (X3 P2 03. Long-range NOEs indicate that P1 and P3 interact with each other. Site-directed mutagenesis was used to identify residues in 0, 03 and the loop connecting 02 to 03 that affect Z-DNA binding. Also identified were I I hydrophobic residues that are essential for protein stability. Comparison with known structures reveals some similarity between Z,,, and (oc + 0) helix-tum-helix proteins, such as histone 5 and the family of hepatocyte nuclear factor-3 winged-helix-tum-helix transcription factors. Taken together, the structural and functional data suggest that recognition of Z-DNA by Z,,, involves residues in both the 0 helix and the C-terminal P-sheet.