The structures of non-CG-repeat Z-DNAs co-crystallized with the Z-DNA-binding domain, hZ alpha(ADAR1).
The Z-DNA conformation preferentially occurs at alternating purine-pyrimidine repeats, and is specifically recognized by Z alpha domains identified in several Z-DNA-binding proteins. The binding of Z alpha to foreign or chromosomal DNA in various sequence contexts is known to influence various biological functions, including the DNA-mediated innate immune response and transcriptional modulation of gene expression. For these reasons, understanding its binding mode and the conformational diversity of Z alpha bound Z-DNAs is of considerable importance. However, structural studies of Z alpha bound Z-DNA have been mostly limited to standard CG-repeat DNAs. Here, we have solved the crystal structures of three representative non-CG repeat DNAs, d(CACGTG)(2), d(CGTACG)(2) and d(CGGCCG)(2) complexed to hZ alpha(ADAR1) and compared those structures with that of hZ alpha(ADAR1)/d(CGCGCG)(2) and the Z alpha-free Z-DNAs. hZ alpha(ADAR1) bound to each of the three Z-DNAs showed a well conserved binding mode with very limited structural deviation irrespective of the DNA sequence, although varying numbers of residues were in contact with Z-DNA. Z-DNAs display less structural alterations in the Z alpha-bound state than in their free form, thereby suggesting that conformational diversities of Z-DNAs are restrained by the binding pocket of Z alpha. These data suggest that Z-DNAs are recognized by Z alpha through common conformational features regardless of the sequence and structural alterations.
Ha
Sung Chul
SC
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Choi
Jongkeun
J
Hwang
Hye-Yeon
HY
Rich
Alexander
A
Kim
Yang-Gyun
YG
Kim
Kyeong Kyu
KK
D000243:Adenosine Deaminase / Q000737:chemistry*; D018360:Crystallography, X-Ray; D043542:DNA, Z-Form / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D016601:RNA-Binding Proteins; D012091:Repetitive Sequences, Nucleic Acid
D043542:DNA, Z-Form; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase