The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand

The action of 1 alpha,25-dihydroxyvitamin D-3 is mediated by its nuclear re ceptor (VDR), a ligand-dependent transcription regulator. We report the 1.8 Angstrom resolution crystal structure of the complex between a VDR ligand- binding domain (LBD) construct lacking the highly variable VDR-specific ins ertion domain and vitamin D. The construct exhibits the same binding affini ty for vitamin D and transactivation ability as the wild-type protein, show ing that the N-terminal part of the LBD is essential for its structural and functional integrity while the large insertion peptide is dispensable. The structure reveals the active conformation of the bound ligand and allows u nderstanding of the different binding properties of some synthetic analogs.