The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand.
The action of 1 alpha, 25-dihydroxyvitamin D3 is mediated by its nuclear receptor (VDR), a ligand-dependent transcription regulator. We report the 1.8 A resolution crystal structure of the complex between a VDR ligand-binding domain (LBD) construct lacking the highly variable VDR-specific insertion domain and vitamin D. The construct exhibits the same binding affinity for vitamin D and transactivation ability as the wild-type protein, showing 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 understanding of the different binding properties of some synthetic analogs.
Rochel
N
N
Laboratoire de Biologie Structurale, Institut de Génétique et de Biologie Moléculaire et Cellulaire CNRS/INSERM/ULP, Illkirch, France.
Wurtz
J M
JM
Mitschler
A
A
Klaholz
B
B
Moras
D
D
D000595:Amino Acid Sequence; D002117:Calcitriol / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray / Q000379:methods; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D018167:Receptors, Calcitriol / Q000737:chemistry* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D008024:Ligands; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D002117:Calcitriol