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
January 2002
Article
| Related Files |
|---|
View PDF Version
(12444966.pdf, 0.4MB) |
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.
- Animals
- Research Support, Non-U.S. Gov't
- Amino Acid Sequence
- Base Sequence
- CHO Cells
- DNA Primers
- Ligands
- *Amino Acid Motifs
- Amino Acids/chemistry/*metabolism
- Binding Sites
- Cricetinae
- Receptors, Androgen/chemistry/*metabolism
- Sequence Homology, Amino Acid
- interaction
- receptor
- n /c interaction
- protein
- androgen
- yeast
- domain
- motif
- androgen receptor
- ar lbd
- function
- system
- assay
- ar ntd
- coactivator
- protein interaction system
- fragment
- 1 lm dht
- expression
- activity
