Structure of the homodimeric androgen receptor ligand-binding domain.

ABSTRACT: The androgen receptor (AR) plays a crucial role in normal physiology, development and metabolism as well as in the aetiology and treatment of diverse pathologies such as androgen insensitivity syndromes (AIS), male infertility and prostate cancer (PCa). Here we show that dimerization of AR ligand-binding domain (LBD) is induced by receptor agonists but not by antagonists. The 2.15-Šcrystal structure of homodimeric, agonist- and coactivator peptide-bound AR-LBD unveils a 1,000-Ų large dimerization surface, which harbours over 40 previously unexplained AIS- and PCa-associated point mutations. An AIS mutation in the self-association interface (P767A) disrupts dimer formation in vivo, and has a detrimental effect on the transactivating properties of full-length AR, despite retaine

SUBMITTER: Nadal M 

PROVIDER: S-EPMC5303882 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature