Hormone-Dependent Coactivator Binding to a Hydrophobic Cleft on Nuclear Receptors

摘要

The ligand-binding domain of nuclear receptors contains a transcriptional activation function (AF-2) that mediates hormone-dependent binding of coactivator proteins. Scna- ning surface mutagenesis on the human thyroid hormone receptor was performed to define the site binds the coactivator 1 (SRC-1). The residues involved encircle a small surface that contains a hydrophobic cleft. Ligand activation of transcription in- volves formation of this surface by folding the carboxyl-terminal α helix against a scaffold volves formation of this surface by folding the carboxyl-terminal α helix against a scaffold of three other helices. These features may represent general ones for nuclear receptors.