Androgen receptor

Function

Androgen receptor (AR) is a nuclear receptor which is activated by testosterone or 5-α-dihydrotestosterone (DHT) hormone. Upon binding the androgenic hormone it translocates to the nucleus where it acts as a DNA-binding transcription factor. The AR binds to a specific sequence of DNA called hormone response element. AR binds to other proteins in the nucleus causing up- or down gene regulation. AR exists in two isoforms. AR-B is full length 110 kDa and AR-A (87 kDa) lacks the N-terminal 187 amino acids.

Disease

Mutated AR is involved in male infertility and prostate cancer. In healthy people, one region of the AR gene shows upto 36 repeats of the CAG sequence. Patients with abnormally high number of CAG repeats can develop spinal muscular atrophy.

Structural highlights

AR structure is composed of 5 domains -
A/B: N-terminal regulatory domain contains activation function 1 (residues 101-370), activation function 5 (residues 360-485) and dimerization surface (residues 1-36 and 370-494).
C: DNA binding domain (DBD)
D: Hinge region between DBD and LBD
E: Ligand binding domain (LBD) containing an which binds intramolecularly the N-terminal FXXFL motif or coactivators with the same motif.^[1] Water molecules are shown as red spheres.
F: C-terminal domain

3D Structures of androgen receptor

Androgen receptor 3D structures