Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors.
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.
Feng
W
W
Metabolic Research Unit, Box 0540, University of California San Francisco, San Francisco, CA 94143-0540, USA.
Ribeiro
R C
RC
Wagner
R L
RL
Nguyen
H
H
Apriletti
J W
JW
Fletterick
R J
RJ
Baxter
J D
JD
Kushner
P J
PJ
West
B L
BL
D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
D008024:Ligands; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1