Abstract
The nuclear hormone receptors form the largest known family of transcription factors. The current notion of receptor DNA discrimination, based solely on one major type of hexameric half-site and a highly conserved 66-residue core DNA-binding domain (DBD), does not adequately describe how more than 150 nonsteroid receptors differentiate among response elements. Here, we describe the 2.3 A crystal structure of the DNA-binding region of the orphan receptor RevErb arranged as a tandem homodimer on its optimal response element. The structure reveals the presence of a second major protein-DNA interface adjacent to the classical one involving the half-sites. A sequence comparison of orphan receptors suggests that unique minor-groove interactions involving the receptor hinge regions impart the necessary DNA and dimerization specificity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites / physiology
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Conserved Sequence
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Crystallography
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DNA / chemistry
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DNA / metabolism
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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Humans
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Image Processing, Computer-Assisted
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Molecular Sequence Data
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Receptor Subfamily 1, Group D, Member 1
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Nucleic Acid Conformation*
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Proteins / chemistry*
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Proteins / genetics
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Receptors, Cytoplasmic and Nuclear*
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Receptors, Steroid / chemistry*
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Receptors, Steroid / genetics
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Sequence Homology, Amino Acid
Substances
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DNA-Binding Proteins
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NR1D1 protein, human
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Nuclear Proteins
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Nuclear Receptor Subfamily 1, Group D, Member 1
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Proteins
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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DNA