Intra-domain Communication Between the N-Terminal and DNA-binding Domains of the Androgen Receptor: Modulation of Androgen Response Element DNA Binding.

Jacqueline Brodie, Iain Joseph McEwan

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The androgen receptor (AR) is a ligand-activated transcription factor that recognises and binds to specific DNA response elements upon activation by the steroids testosterone or dihydrotestosterone. In vitro, two types of response element have been characterised - non-selective elements that bind the androgen, glucocorticoid and progesterone receptors, and androgen receptor-selective sequences. In the present study, the allosteric effects of DNA binding on the receptor amino-terminal domain (NTD) were studied. Binding to both types of DNA response element resulted in changes in the intrinsic fluorescence emission spectrum for four tryptophan residues within the AR-NTD and resulted in a more protease-resistant conformation. In binding experiments, it was observed that the presence of the AR-NTD reduced the affinity of receptor polypeptides for binding to both selective and non-selective DNA elements derived from the probasin, PEM and prostatin C3 genes respectively, without significantly altering the protein-base pair contacts. Taken together, these results highlight the role of intra-domain communications between the AR-NTD and the DNA binding domain in receptor structure and function.

Original languageEnglish
Pages (from-to)603-615
Number of pages12
JournalJournal of Molecular Endocrinology
Volume34
DOIs
Publication statusPublished - 2005

Keywords

  • ESTROGEN-RECEPTOR
  • GLUCOCORTICOID-RECEPTORS
  • ALLOSTERIC MODULATION
  • GENE-EXPRESSION
  • AMINO-ACIDS
  • CONFORMATION
  • PROTEIN
  • SPECIFICITY
  • REGION
  • IDENTIFICATION

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