Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-alpha

William Bourguet , Marc Ruff (1, 2) , Pierre Chambon (2, 1) , Hinrich Gronemeyer (2, 1) , Dino Moras (1, 2)

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

The crystal structure of the human retinoid-X receptor RXR-alpha ligand-binding domain reveals a previously undiscovered fold of an antiparallel alpha-helical sandwich, packed as dimeric units. Two helices and one loop form the homodimerization surface, and hydrophobic heptad repeats participate in stabilizing the fold. The existence of a ligand-binding pocket is proposed that would allow 9-cis retinoic acid to interact with different functional modules, including the AF-2 activating domain. Several lines of evidence indicate that the overall structure is a prototype fold of ligand-binding domains of nuclear receptors.

Domaines: Biochimie, Biologie Moléculaire

William Bourguet, Marc Ruff, Pierre Chambon, Hinrich Gronemeyer, Dino Moras. Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-alpha. Nature, 1995, 375 (6530), pp.377-382. ⟨10.1038/375377a0⟩. ⟨hal-03832776⟩