Open AccessAmino acids 3–13 and amino acids in and flanking the 23 FxxLF 27 motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor
Author(s) -
Steketee Karine,
Berrevoets Cor A,
Dubbink Hendrikus J.,
Doesburg Paul,
Hersmus Remko,
Brinkmann Albert O.,
Trapman Jan
Publication year - 2002
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2002.03276.x
Subject(s) - amino acid , stereochemistry , amino terminal , chemistry , ligand (biochemistry) , peptide sequence , biochemistry , receptor , gene
The N‐terminal domain (NTD) and the ligand‐binding domain (LBD) of the androgen receptor (AR) exhibit a ligand–dependent interaction (N/C interaction). Amino acids 3–36 in the NTD (AR 3−36 ) play a dominant role in this interaction. Previously, it has been shown that a ΦxxΦΦ motif in AR 3−36 , 23 FxxLF 27 , is essential for LBD interaction. We demonstrate in the current study that AR 3−36 can be subdivided into two functionally distinct fragments: AR 3−13 and AR 16−36 . AR 3−13 does not directly interact with the AR LBD, but rather contributes to the transactivation function of the AR.NTD‐AR.LBD complex. AR 16−36, encompassing the 23 FxxLF 27 motif, is predicted to fold into a long amphipathic α‐helix. A second ΦxxΦΦ candidate protein interaction motif within the helical structure, 30 VREVI 34 , shows no affinity to the LBD. Within AR 16−36 , amino acid residues in and flanking the 23 FxxLF 27 motif are demonstrated to modulate N/C interaction. Substitution of Q24 and N25 by alanine residues enhances N/C interaction. Substitution of amino acids flanking the 23 FxxLF 27 motif by alanines are inhibitory to LBD interaction.