The structures of non-CG-repeat Z-DNAs co-crystallized with the Z-DNA-binding domain, hZαADAR1

• Main Authors: Ha, Sung Chul (Author), Choi, Jongkeun (Author), Hwang, Hye-Yeon (Author), Rich, Alexander (Contributor), Kim, Yang-Gyun (Author), Kim, Kyeong Kyu (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor)
• Format: Article
• Language: English
• Published: Oxford University Press, 2012-09-17T20:26:58Z.
• Subjects: Article
• Online Access: Get fulltext

 The Z-DNA conformation preferentially occurs at alternating purine-pyrimidine repeats, and is specifically recognized by Zα domains identified in several Z-DNA-binding proteins. The binding of Zα 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 Zα bound Z-DNAs is of considerable importance. However, structural studies of Zα 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 hZαADAR1 and compared those structures with that of hZαADAR1/d(CGCGCG)2 and the Zα-free Z-DNAs. hZαADAR1 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 Zα-bound state than in their free form, thereby suggesting that conformational diversities of Z-DNAs are restrained by the binding pocket of Zα. These data suggest that Z-DNAs are recognized by Zα through common conformational features regardless of the sequence and structural alterations.