title: Ligand affinity, homodimerization, and ligand-induced secondary structural change of the human vitamin d receptor.
abstract: The intrinsic tryptophan fluorescence signal of the full-length nuclear receptor hVDR was used to directly determine the dissociation constants, K(d), of two ligands yielding K(d) = 32 nM for 1alpha,25(OH)(2)D(3) and K(d) = 322 nM for 25(OH)D(3). Ligand binding was accompanied by a conformational change in the alpha-helical part of hVDR as revealed by CD spectroscopy. In addition, the presence of calcitriol was found to be a necessary prerequisite for the homodimerisation of hVDR which was monitored using fluorescence anisotropy. We conclude that the observed ligand-induced structural change of hVDR is conditional for dimerisation of the protein.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Graz, Universitätsplatz 1, Graz, A-8010, Austria.
authors.forename: S F
authors.initials: SF
authors.lastname: Falsone
authors.forename: R
authors.initials: R
authors.lastname: Kurkela
authors.forename: G
authors.initials: G
authors.lastname: Chiarandini
authors.forename: P
authors.initials: P
authors.lastname: Vihko
authors.forename: A J
authors.initials: AJ
authors.lastname: Kungl
mesh_terms: D002112:Calcifediol / Q000737:chemistry / Q000494:pharmacology; D002117:Calcitriol / Q000737:chemistry; D002942:Circular Dichroism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005454:Fluorescence Polarization; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011487:Protein Conformation / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000737:chemistry* / Q000502:physiology; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: C116441:2-methyl-1,25-dihydroxyvitamin D3; D008024:Ligands; D018167:Receptors, Calcitriol; D014807:Vitamin D; D002117:Calcitriol; D002112:Calcifediol