Intra-domain communication between the N-terminal and DNA-binding domains of the androgen receptor: modulation of androgen response element DNA binding.
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.
Brodie
Jacqueline
J
School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
McEwan
Iain J
IJ
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D006868:Hydrolysis; D011487:Protein Conformation; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D017931:DNA Primers; D011944:Receptors, Androgen; D004247:DNA