title: The androgen receptor transactivation domain: the interplay between protein conformation and protein-protein interactions.
abstract: The AR (androgen receptor) belongs to the nuclear receptor superfamily and directly regulates patterns of gene expression in response to the steroids testosterone and dihydrotestosterone. Sequences within the large N-terminal domain of the receptor have been shown to be important for transactivation and protein-protein interactions; however, little is known about the structure and folding of this region. Folding of the AR transactivation domain was observed in the presence of the helix-stabilizing solvent trifluorethanol and the natural osmolyte TMAO (trimethylamine N-oxide). TMAO resulted in the movement of two tryptophan residues to a less solvent-exposed environment and the formation of a protease-resistant conformation. Critically, binding to a target protein, the RAP74 subunit of the general transcription factor TFIIF, resulted in a similar resistance to protease digestion, consistent with induced folding of the receptor transactivation domain. Our current hypothesis is that the folding of the transactivation domain in response to specific protein-protein interactions creates a platform for subsequent interactions, resulting in the formation of a competent transcriptional activation complex.
mesh_terms: D006728:Hormones / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008744:Methylamines / Q000737:chemistry; D008954:Models, Biological; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D006728:Hormones; D008024:Ligands; D008744:Methylamines; D011944:Receptors, Androgen; D014157:Transcription Factors; C005855:trimethyloxamine