Abstract
The ligand-binding domain of nuclear receptors contains a transcriptional activation function (AF-2) that mediates hormone-dependent binding of coactivator proteins. Scanning surface mutagenesis on the human thyroid hormone receptor was performed to define the site that binds the coactivators, glucocorticoid receptor-interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1). The residues involved encircle a small surface that contains a hydrophobic cleft. Ligand activation of transcription involves formation of this surface by folding the carboxyl-terminal alpha helix against a scaffold of three other helices. These features may represent general ones for nuclear receptors.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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HeLa Cells
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Histone Acetyltransferases
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Humans
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Ligands
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Models, Molecular
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Mutagenesis, Site-Directed
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Nuclear Receptor Coactivator 1
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Nuclear Receptor Coactivator 2
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Protein Conformation
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Protein Folding
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Protein Structure, Secondary
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Receptors, Retinoic Acid / metabolism
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Receptors, Thyroid Hormone / chemistry*
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Receptors, Thyroid Hormone / genetics
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Receptors, Thyroid Hormone / metabolism*
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Recombinant Fusion Proteins / metabolism
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Retinoid X Receptors
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Transcription Factors / metabolism*
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Transcriptional Activation*
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Triiodothyronine / metabolism*
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Triiodothyronine / pharmacology
Substances
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Ligands
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NCOA2 protein, human
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Nuclear Receptor Coactivator 2
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Recombinant Fusion Proteins
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Retinoid X Receptors
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Transcription Factors
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Triiodothyronine
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Histone Acetyltransferases
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NCOA1 protein, human
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Nuclear Receptor Coactivator 1