Amino acids 3-13 and amino acids in and flanking the 23FxxLF27 motif modulate the interaction between the N-terminal and ligand-binding domain of the androgen receptor
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 (AR3-36) play a dominant role in
this interaction. Previously, it has been shown that a PhixxPhiPhi motif
in AR3-36, 23FxxLF27, is essential for LBD interaction. We demonstrate in
the current study that AR3-36 can be subdivided into two functionally
distinct fragments: AR3-13 and AR16-36. AR3-13 does not directly interact
with the AR LBD, but rather contributes to the transactivation function of
the AR.NTD-AR.LBD complex. AR16-36, encompassing the 23FxxLF27 motif, is
predicted to fold into a long amphipathic alpha-helix. A second
PhixxPhiPhi candidate protein interaction motif within the helical
structure, 30VREVI34, shows no affinity to the LBD. Within AR16-36, amino
acid residues in and flanking the 23FxxLF27 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
23FxxLF27 motif by alanines are inhibitory to LBD interaction