Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone

The structures of the ligand-binding domains (LBD) of the wildtype androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, b oth bound to dihydrotestosterone. have been refined at 2.0 Angstrom resolut ion. In contrast to the homodimer seen in the retinoid-X receptor and estro gen receptor LED structures, the AR LED is monomeric, possibly because of t he extended C terminus of AR, which lies in a groove at the dimerization in terface. Binding of the natural ligand dihydrotestosterone by the mutant LE D involves interactions with the same residues as in the wildtype receptor, with the exception of the side chain of threonine 877, which is an alanine residue in the mutant. This structural difference in the binding pocket ca n explain the ability of the mutant AR found in LNCaP cells (T877A) to acco mmodate progesterone and other ligands that the wild-type receptor cannot.