Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 11 June 1999:
Vol. 284. no. 5421, pp. 1841 - 1845
DOI: 10.1126/science.284.5421.1841
Prev | Table of Contents | Next

Reports

Crystal Structure of the Zalpha Domain of the Human Editing Enzyme ADAR1 Bound to Left-Handed Z-DNA

Thomas Schwartz, 1 Mark A. Rould, 2 Ky Lowenhaupt, 1 Alan Herbert, 1 Alexander Rich 1*

The editing enzyme double-stranded RNA adenosine deaminase includes a DNA binding domain, Zalpha , which is specific for left-handed Z-DNA. The 2.1 angstrom crystal structure of Zalpha complexed to DNA reveals that the substrate is in the left-handed Z conformation. The contacts between Zalpha and Z-DNA are made primarily with the "zigzag" sugar-phosphate backbone, which provides a basis for the specificity for the Z conformation. A single base contact is observed to guanine in the syn conformation, characteristic of Z-DNA. Intriguingly, the helix-turn-helix motif, frequently used to recognize B-DNA, is used by Zalpha to contact Z-DNA.

1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USA.
*   To whom correspondence should be addressed.

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Base extrusion is found at helical junctions between right- and left-handed forms of DNA and RNA.
D. Kim, S. Reddy, D. Y. Kim, A. Rich, S. Lee, K. K. Kim, and Y.-G. Kim (2009)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Human genomic Z-DNA segments probed by the Z{alpha} domain of ADAR1.
H. Li, J. Xiao, J. Li, L. Lu, S. Feng, and P. Droge (2009)
Nucleic Acids Res. 37, 2737-2746
   Abstract »    Full Text »    PDF »
The structures of non-CG-repeat Z-DNAs co-crystallized with the Z-DNA-binding domain, hZ{alpha}ADAR1.
S. C. Ha, J. Choi, H.-Y. Hwang, A. Rich, Y.-G. Kim, and K. K. Kim (2009)
Nucleic Acids Res. 37, 629-637
   Abstract »    Full Text »    PDF »
The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in complex with Z-DNA reveals an unusual binding mode to Z-DNA.
S. C. Ha, D. Kim, H.-Y. Hwang, A. Rich, Y.-G. Kim, and K. K. Kim (2008)
PNAS 105, 20671-20676
   Abstract »    Full Text »    PDF »
The Human Monocytic Leukemia Zinc Finger Histone Acetyltransferase Domain Contains DNA-binding Activity Implicated in Chromatin Targeting.
M. A. Holbert, T. Sikorski, J. Carten, D. Snowflack, S. Hodawadekar, and R. Marmorstein (2007)
J. Biol. Chem. 282, 36603-36613
   Abstract »    Full Text »    PDF »
Characterization of DNA-binding activity of Z{alpha} domains from poxviruses and the importance of the -wing regions in converting B-DNA to Z-DNA.
D. Van Quyen, S. C. Ha, K. Lowenhaupt, A. Rich, K. K. Kim, and Y.-G. Kim (2007)
Nucleic Acids Res. 35, 7714-7720
   Abstract »    Full Text »    PDF »
HIF-1 regulates heritable variation and allele expression phenotypes of the macrophage immune response gene SLC11A1 from a Z-DNA forming microsatellite.
H. K. Bayele, C. Peyssonnaux, A. Giatromanolaki, W. W. Arrais-Silva, H. S. Mohamed, H. Collins, S. Giorgio, M. Koukourakis, R. S. Johnson, J. M. Blackwell, et al. (2007)
Blood 110, 3039-3048
   Abstract »    Full Text »    PDF »
A peptide with alternating lysines can act as a highly specific Z-DNA binding domain.
Y.-G. Kim, H.-J. Park, K. K. Kim, K. Lowenhaupt, and A. Rich (2006)
Nucleic Acids Res. 34, 4937-4942
   Abstract »    Full Text »    PDF »
ZBP1 subcellular localization and association with stress granules is controlled by its Z-DNA binding domains.
N. Deigendesch, F. Koch-Nolte, and S. Rothenburg (2006)
Nucleic Acids Res. 34, 5007-5020
   Abstract »    Full Text »    PDF »
Structure and function of the SWIRM domain, a conserved protein module found in chromatin regulatory complexes.
G. Da, J. Lenkart, K. Zhao, R. Shiekhattar, B. R. Cairns, and R. Marmorstein (2006)
PNAS 103, 2057-2062
   Abstract »    Full Text »    PDF »
A Novel Plant-Specific Family Gene, ROOT PRIMORDIUM DEFECTIVE 1, Is Required for the Maintenance of Active Cell Proliferation.
M. Konishi and M. Sugiyama (2006)
Plant Physiology 140, 591-602
   Abstract »    Full Text »    PDF »
Modulation of ADAR1 editing activity by Z-RNA in vitro.
M. Koeris, L. Funke, J. Shrestha, A. Rich, and S. Maas (2005)
Nucleic Acids Res. 33, 5362-5370
   Abstract »    Full Text »    PDF »
Biological function of the vaccinia virus Z-DNA-binding protein E3L: Gene transactivation and antiapoptotic activity in HeLa cells.
J.-A. Kwon and A. Rich (2005)
PNAS 102, 12759-12764
   Abstract »    Full Text »    PDF »
A PKR-like eukaryotic initiation factor 2{alpha} kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains.
S. Rothenburg, N. Deigendesch, K. Dittmar, F. Koch-Nolte, F. Haag, K. Lowenhaupt, and A. Rich (2005)
PNAS 102, 1602-1607
   Abstract »    Full Text »    PDF »
Distributions of Z-DNA and nuclear factor I in human chromosome 22: a model for coupled transcriptional regulation.
P. C. Champ, S. Maurice, J. M. Vargason, T. Camp, and P. S. Ho (2004)
Nucleic Acids Res. 32, 6501-6510
   Abstract »    Full Text »    PDF »
A poxvirus protein forms a complex with left-handed Z-DNA: Crystal structure of a Yatapoxvirus Z{alpha} bound to DNA.
S. C. Ha, N. K. Lokanath, D. Van Quyen, C. A. Wu, K. Lowenhaupt, A. Rich, Y.-G. Kim, and K. K. Kim (2004)
PNAS 101, 14367-14372
   Abstract »    Full Text »    PDF »
Interaction of the Z{alpha} domain of human ADAR1 with a negatively supercoiled plasmid visualized by atomic force microscopy.
A. Y. Lushnikov, B. A. Brown II, E. A. Oussatcheva, V. N. Potaman, R. R. Sinden, and Y. L. Lyubchenko (2004)
Nucleic Acids Res. 32, 4704-4712
   Abstract »    Full Text »    PDF »
Crystal Structure of Human eIF3k, the First Structure of eIF3 Subunits.
Z. Wei, P. Zhang, Z. Zhou, Z. Cheng, M. Wan, and W. Gong (2004)
J. Biol. Chem. 279, 34983-34990
   Abstract »    Full Text »    PDF »
The solution structure of the N-terminal domain of E3L shows a tyrosine conformation that may explain its reduced affinity to Z-DNA in vitro.
J. D. Kahmann, D. A. Wecking, V. Putter, K. Lowenhaupt, Y.-G. Kim, P. Schmieder, H. Oschkinat, A. Rich, and M. Schade (2004)
PNAS 101, 2712-2717
   Abstract »    Full Text »    PDF »
Evidence that vaccinia virulence factor E3L binds to Z-DNA in vivo: Implications for development of a therapy for poxvirus infection.
Y.-G. Kim, K. Lowenhaupt, D.-B. Oh, K. K. Kim, and A. Rich (2004)
PNAS 101, 1514-1518
   Abstract »    Full Text »    PDF »
A role for Z-DNA binding in vaccinia virus pathogenesis.
Y.-G. Kim, M. Muralinath, T. Brandt, M. Pearcy, K. Hauns, K. Lowenhaupt, B. L. Jacobs, and A. Rich (2003)
PNAS 100, 6974-6979
   Abstract »    Full Text »    PDF »
Elevated activity of the large form of ADAR1 in vivo: Very efficient RNA editing occurs in the cytoplasm.
S. K. WONG, S. SATO, and D. W. LAZINSKI (2003)
RNA 9, 586-598
   Abstract »    Full Text »    PDF »
Z-DNA-binding proteins can act as potent effectors of gene expression invivo.
D.-B. Oh, Y.-G. Kim, and A. Rich (2002)
PNAS 99, 16666-16671
   Abstract »    Full Text »    PDF »
Nucleocytoplasmic Distribution of Human RNA-editing Enzyme ADAR1 Is Modulated by Double-stranded RNA-binding Domains, a Leucine-rich Export Signal, and a Putative Dimerization Domain.
A. Strehblow, M. Hallegger, and M. F. Jantsch (2002)
Mol. Biol. Cell 13, 3822-3835
   Abstract »    Full Text »    PDF »
Having it both ways: transcription factors that bind DNA and RNA.
L. A. Cassiday and L. J. Maher III (2002)
Nucleic Acids Res. 30, 4118-4126
   Abstract »    Full Text »    PDF »
The Bacterial Histone-like Protein HU Specifically Recognizes Similar Structures in All Nucleic Acids. DNA, RNA, AND THEIR HYBRIDS.
A. Balandina, D. Kamashev, and J. Rouviere-Yaniv (2002)
J. Biol. Chem. 277, 27622-27628
   Abstract »    Full Text »    PDF »
Complex regulation of the human gene for the Z-DNA binding protein DLM-1.
S. Rothenburg, T. Schwartz, F. Koch-Nolte, and F. Haag (2002)
Nucleic Acids Res. 30, 993-1000
   Abstract »    Full Text »    PDF »
CRM1 Mediates the Export of ADAR1 through a Nuclear Export Signal within the Z-DNA Binding Domain.
H. Poulsen, J. Nilsson, C. K. Damgaard, J. Egebjerg, and J. Kjems (2001)
Mol. Cell. Biol. 21, 7862-7871
   Abstract »    Full Text »    PDF »
The Zalpha domain of the editing enzyme dsRNA adenosine deaminase binds left-handed Z-RNA as well as Z-DNA.
B. A. Brown II, K. Lowenhaupt, C. M. Wilbert, E. B. Hanlon, and A. Rich (2000)
PNAS
   Abstract »    Full Text »
Allosteric, chiral-selective drug binding to DNA.
X. Qu, J. O. Trent, I. Fokt, W. Priebe, and J. B. Chaires (2000)
PNAS
   Abstract »    Full Text »
The solution structure of the Zalpha domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA.
M. Schade, C. J. Turner, R. Kuhne, P. Schmieder, K. Lowenhaupt, A. Herbert, A. Rich, and H. Oschkinat (1999)
PNAS 96, 12465-12470
   Abstract »    Full Text »    PDF »
The Zab Domain of the Human RNA Editing Enzyme ADAR1 Recognizes Z-DNA When Surrounded by B-DNA.
Y.-G. Kim, K. Lowenhaupt, S. Maas, A. Herbert, T. Schwartz, and A. Rich (2000)
J. Biol. Chem. 275, 26828-26833
   Abstract »    Full Text »    PDF »
From the Cover: Allosteric, chiral-selective drug binding to DNA.
X. Qu, J. O. Trent, I. Fokt, W. Priebe, and J. B. Chaires (2000)
PNAS 97, 12032-12037
   Abstract »    Full Text »    PDF »
The Zalpha domain of the editing enzyme dsRNA adenosine deaminase binds left-handed Z-RNA as well as Z-DNA.
B. A. Brown II, K. Lowenhaupt, C. M. Wilbert, E. B. Hanlon, and A. Rich (2000)
PNAS 97, 13532-13536
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)