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.
Skip Nav Destination
Article navigation
October 2003
- PDF Icon PDF LinkFront Matter
Conference Article|
October 01 2003
The androgen receptor transactivation domain: the interplay between protein conformation and protein–protein interactions
J. Reid;
J. Reid
1
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, U.K.
Search for other works by this author on:
R. Betney;
R. Betney
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, U.K.
Search for other works by this author on:
K. Watt;
K. Watt
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, U.K.
Search for other works by this author on:
I.J. McEwan
I.J. McEwan
2
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, U.K.
2To whom correspondence should be addressed (e-mail iain.mcewan@abdn.ac.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (5): 1042–1046.
Citation
J. Reid, R. Betney, K. Watt, I.J. McEwan; The androgen receptor transactivation domain: the interplay between protein conformation and protein–protein interactions. Biochem Soc Trans 1 October 2003; 31 (5): 1042–1046. doi: https://doi.org/10.1042/bst0311042
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.