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.
|Keywords||*Amino Acid Motifs, Amino Acid Sequence, Amino Acids/chemistry/*metabolism, Animals, Base Sequence, Binding Sites, CHO Cells, Cricetinae, DNA Primers, Ligands, Receptors, Androgen/chemistry/*metabolism, Research Support, Non-U.S. Gov't, Sequence Homology, Amino Acid|
Steketee, K., Berrevoets, C.A., Dubbink, H.J., Doesburg, P., Hersmus, R., Brinkmann, A.O., & Trapman, J.. (2002). 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. European Journal of Biochemistry. Retrieved from http://hdl.handle.net/1765/10020