Résumé
The crystal structure of a heterodimer between the ligand-binding domains (LBDs) of the human RARα bound to a selective antagonist and the constitutively active mouse RXRαF318A mutant shows that, pushed by a bulky extension of the ligand, RARα helix H12 adopts an antagonist position. The unexpected presence of a fatty acid in the ligand-binding pocket of RXRαF318A is likely to account for its apparent “constitutivity.” Specific conformational changes suggest the structural basis of pure and partial antagonism. The RAR–RXR heterodimer interface is similar to that observed in most nuclear receptor (NR) homodimers. A correlative analysis of 3D structures and sequences provides a novel view on dimerization among members of the nuclear receptor superfamily.