The androgen receptor transactivation domain: the interplay between protein conformation and protein-protein interactions

Janet Elizabeth Reid, Russell Betney, K. Watt, Iain Joseph McEwan

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1042-1046
Number of pages4
JournalBiochemical Society Transactions
Volume31
Issue numberPt 5
Publication statusPublished - 2003

Keywords

  • fluorescence spectroscopy
  • mutagenesis
  • secondary-structure prediction
  • steroid receptor
  • transactivation
  • AMINO-TERMINAL DOMAIN
  • HUMAN GLUCOCORTICOID-RECEPTOR
  • TRANSCRIPTION FACTOR TFIIF
  • LIGAND-BINDING DOMAIN
  • STEROID-RECEPTORS
  • ACTIVATION
  • SPECIFICITY
  • SEQUENCE
  • REGIONS
  • DETERMINANTS

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