Nucleic Acids Research Advance Access originally published online on December 11, 2008
Nucleic Acids Research 2009 37(2):629-637; doi:10.1093/nar/gkn976
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Nucleic Acids Research, 2009, Vol. 37, No. 2 629-637
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
The structures of non-CG-repeat Z-DNAs co-crystallized with the Z-DNA-binding domain, hZ
ADAR1
1Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea, 2Department of Biology, Massachusetts Institute of technology, Cambridge, Massachusetts 02139, USA and 3Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea
*To whom correspondence should be addressed. Tel: +82 31 299 6136; Fax: +82 31 299 6159; Email: kkim{at}med.skku.ac.kr
Correspondence may also be addressed to Yang-Gyun Kim, Tel: +82 31 299 4563; Fax: +82 31 299 4575; Email: ygkimmit{at}skku.edu
Received October 17, 2008. Revised November 19, 2008. Accepted November 19, 2008.
The Z-DNA conformation preferentially occurs at alternating purine-pyrimidine repeats, and is specifically recognized by Z
domains identified in several Z-DNA-binding proteins. The binding of Z 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 bound Z-DNAs is of considerable importance. However, structural studies of Z 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 hZADAR1 and compared those structures with that of hZADAR1/d(CGCGCG)2 and the Z-free Z-DNAs. hZADAR1 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-bound state than in their free form, thereby suggesting that conformational diversities of Z-DNAs are restrained by the binding pocket of Z. These data suggest that Z-DNAs are recognized by Z through common conformational features regardless of the sequence and structural alterations.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID codes of hZ
ADAR1 in complex with d(CACGTG)2, d(CGTACG)2 and d(CGGCCG)2 are 3F21,3F22 and 3F23, respectively)