A STRUCTURAL VIEW OF LIGAND-BINDING TO THE RETINOID RECEPTORS

Nuclear receptors play an important role in transcription regulation. They bind as homo- or heterodimers to the response elements of their t arget genes and interact with numerous and diverse partners, e.g. coac tivator and corepressor proteins, and transcription factors. Many of t hese processes are ligand-dependent, i.e. binding of natural ligands a ctivates the nuclear receptor through conformational changes of the pr otein. Synthetic ligands can be made specific for a particular recepto r and have the potential for reducing the side-effects of natural liga nds in pharmaceutical applications. The crystal structures of ligand-b inding domains of the retinoid receptors have brought the first insigh t into the spatial organization and the nature of the ligand-induced c hanges at the atomic level. Furthermore, these structures provide a st arting point for structure-based drug design of retinoids.