The human androgen receptor AF1 transactivation domain: interactions with transcription factor IIF and molten-globule-like structural characteristics

D. N. Lavery, Iain Joseph McEwan

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The AR (androgen receptor) is a ligand-activated transcription factor and member of the steroid receptor superfamily. The AR responds to the ligands testosterone and dihydrotestosterone and activates multiple downstream genes required in development and reproduction. During the events of transactivation, the AR makes specific protein-protein interactions with several basal transcription factors such as TBP (TATA-box-binding protein) and TFIIF (transcription factor IIF). These interactions occur predominantly within a defined region termed AF1 (activation function-1) located within the highly disordered N-terminal domain of the receptor. Our focus is on the structural aspects of AF1 and how this flexible and disordered domain generates functional interactions with regulators of transcription. our working hypothesis is that AR-AF1 domain exhibits induced folding when contacted by transcription regulators (such as TFIIF) into a more compact and 'active' conformation, enabling further co-regulator recruitment and ultimately transcription. Structural flexibility and intrinsic disorder of AR-AF1 were studied using predictive algorithms and fluorescence spectroscopy under different experimental conditions and the results revealed this domain retains characteristics indicative of molten-globule or pre-molten-globule-like structures. We hypothesize that this partially folded intermediate state is important for, and enables the AF1 domain to make, multiple protein-protein interactions. The structural aspects of AR-AF1 and interactions with TFIIF are discussed.

Original languageEnglish
Pages (from-to)1054-1057
Number of pages4
JournalBiochemical Society Transactions
Volume34
DOIs
Publication statusPublished - Dec 2006

Keywords

  • basal transcription factor
  • molten globule
  • protein-protein interaction
  • steroid hormone receptor
  • transactivation domain
  • transcription
  • general transcription
  • factor-TFIIF
  • terminl domain
  • protein
  • subunit

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