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Structure of the DLM-1–Z-DNA complex reveals a conserved family of Z-DNA-binding proteins

Nature Structural Biology volume 8, pages 761–765 (2001)Cite this article

Abstract

The first crystal structure of a protein, the Zα high affinity binding domain of the RNA editing enzyme ADAR1, bound to left-handed Z-DNA was recently described. The essential set of residues determined from this structure to be critical for Z-DNA recognition was used to search the database for other proteins with the potential for Z-DNA binding. We found that the tumor-associated protein DLM-1 contains a domain with remarkable sequence similarities to ZαADAR. Here we report the crystal structure of this DLM-1 domain bound to left-handed Z-DNA at 1.85 Å resolution. Comparison of Z-DNA binding by DLM-1 and ADAR1 reveals a common structure-specific recognition core within the binding domain. However, the domains differ in certain residues peripheral to the protein–DNA interface. These structures reveal a general mechanism of Z-DNA recognition, suggesting the existence of a family of winged-helix proteins sharing a common Z-DNA binding motif.

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Figure 1: Protein sequences, domain structure and in vitro Z-DNA binding studies.
Figure 2: Overall structure of the ZαDLM–Z-DNA complex.
Figure 3: Comparison of protein–DNA contacts between ZαDLM and ZαADAR.
Figure 4: Electron density of the ZαDLM–Z-DNA complex.

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Protein Data Bank

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Acknowledgements

We thank S. Rothenburg (Universitätsklinikum Hamburg-Eppendorf) for providing mouse cDNA and for carefully reading the manuscript. Helpful discussions with U. Müller, Y.A. Muller (MDC) and M.A. Rould (UVM) are gratefully acknowledged.

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  1. Thomas Schwartz

    Present address: Laboratory of Cell Biology, The Rockefeller University, New York, New York, 10021, USA

Authors and Affiliations

  1. Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, Berlin, D-13125, Germany

    Thomas Schwartz, Joachim Behlke & Udo Heinemann

  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Ky Lowenhaupt & Alexander Rich

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Correspondence to Thomas Schwartz.

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Schwartz, T., Behlke, J., Lowenhaupt, K. et al. Structure of the DLM-1–Z-DNA complex reveals a conserved family of Z-DNA-binding proteins. Nat Struct Mol Biol 8, 761–765 (2001). https://doi.org/10.1038/nsb0901-761

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