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Structural determinants of nuclear receptor assembly on DNA direct repeats

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Abstract

Nuclear receptor heterodimers recognize response elements composed of two direct repeats of the consensus sequence 5′-AGGTCA-3′ separated by one to five base pairs. The 1.9 Å crystal structure of the complex formed by the DNA-binding domains of the 9-cis retinoic acid receptor and thyroid hormone receptor bound to a thyroid-response element shows that the subunits interact through a DNA-supported interface involving the carboxy-terminal extension of the DNA-binding domain of the thyroid hormone receptor. The stereochemistry suggests a mechanism by which heterodimers recognize the inter-half-site spacing between direct repeats.

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Author notes

  1. Thomas Perlmann

    Present address: Department of Cellular and Molecular Biology, Medical Nobel institute, Karolinska Institute, S17177, Stockholm, Sweden

Authors and Affiliations

  1. Department of Molecular Biophysics and Biochemistry and The Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, 06510, USA

    Fraydoon Rastinejad & Paul B. Sigler

  2. Howard Hughes Medical Institute, Salk Institute, La Jolla, California, 92037, USA

    Thomas Perlmann & Ronald M. Evans

Authors
  1. Fraydoon Rastinejad
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  2. Thomas Perlmann
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  3. Ronald M. Evans
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  4. Paul B. Sigler
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Rastinejad, F., Perlmann, T., Evans, R. et al. Structural determinants of nuclear receptor assembly on DNA direct repeats. Nature 375, 203–211 (1995). https://doi.org/10.1038/375203a0

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