Molecular Cell 2000-02-01

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

W Bourguet, V Vivat, J M Wurtz, P Chambon, H Gronemeyer, D Moras

Index: Mol. Cell. 5(2) , 289-98, (2000)

Full Text: HTML

Abstract

The crystal structure of a heterodimer between the ligand-binding domains (LBDs) of the human RARalpha bound to a selective antagonist and the constitutively active mouse RXRalphaF318A mutant shows that, pushed by a bulky extension of the ligand, RARalpha helix H12 adopts an antagonist position. The unexpected presence of a fatty acid in the ligand-binding pocket of RXRalpha(F318A 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.