Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains

Abstract

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.