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Structure of a TonEBP–DNA complex reveals DNA encircled by a transcription factor

Nature Structural Biology volume 9, pages 90–94 (2002)Cite this article

Abstract

Tonicity-responsive enhancer binding protein (TonEBP), also known as NFAT5, is a unique member of the NFAT family of transcription factors that regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of the NFAT family, TonEBP exists as a homodimer and binds asymmetric TonE DNA sites; furthermore, the affinity of TonEBP for DNA is much lower than that of other NFAT proteins. How TonEBP recognizes the TonE site and regulates the activation of hypertonicity response genes has not been clear. Here we show that TonEBP adopts a NF-κB-like structure upon binding to DNA, providing a direct structural link between the NFAT and NF-κB family of transcription factors. We also show that TonEBP completely encircles its DNA target and present biochemical evidence that the DNA encirclement may lead to increased kinetic stability of the TonEBP–DNA complex. Thus, the list of proteins that bind DNA by encirclement is now expanded to include sequence-specific transcription factors.

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Figure 1: Structure of the TonEBP–DNA complex.
Figure 2: DNA binding by TonEBP.
Figure 3: Dimerization in the TonEBP–DNA complex.
Figure 4: Biochemical analysis of the TonEBP–DNA complex.

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Acknowledgements

The authors thank Z. Ren and H. Tong from APS beamline 14-BM; M. Giffin, G.A. Murphy and D. Theobald for help in data collection; T.R. Cech, O.C. Uhlenbeck and J.A Goodrich for critical reading of the manuscript. This research was supported by a scholar award from the Damon Runyon-Walter Winchell Foundation (L.C.), a grant from the W. M. Keck foundation (L.C.), and an NIH training grant (J.C.S.). C. L.R. is a recipient of a career development Special Fellowship of the Leukemia and Lymphoma Society.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, 80309-0215, Colorado, USA

    James C. Stroud & Lin Chen

  2. The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Cristina Lopez-Rodriguez & Anjana Rao

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  1. James C. Stroud
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Correspondence to Lin Chen.

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Stroud, J., Lopez-Rodriguez, C., Rao, A. et al. Structure of a TonEBP–DNA complex reveals DNA encircled by a transcription factor. Nat Struct Mol Biol 9, 90–94 (2002). https://doi.org/10.1038/nsb749

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