Central role of VDR conformations for understanding selective actions of vitamin D(3) analogues |
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| Authors: | Carlberg C Quack M Herdick M Bury Y Polly P Toell A |
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| Affiliation: | 1. Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary;2. MTA-DE Stem Cells, Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary;3. Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary;4. Department of Biophysics and Cell Biology, University of Debrecen, Debrecen, Hungary;5. MTA-DE Lendület Laboratory of Cellular Metabolism Research Group, Research Center for Molecular Medicine, Department of Medical Chemistry, University of Debrecen, Debrecen, Hungary |
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| Abstract: | The vitamin D(3) receptor (VDR) acts primarily as a heterodimer with the retinoid X receptor (RXR) on different types of 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) response elements (VDREs). Therefore, DNA-bound VDR-RXR heterodimers can be considered as the molecular switches of 1alpha,25(OH)(2)D(3) signalling. Functional conformations of the VDR within these molecular switches appear to be of central importance for describing the biologic actions of 1alpha,25(OH)(2)D(3) and its analogues. Moreover, VDR conformations provide a molecular basis for understanding the potential selective profile of VDR agonists, which is critical for a therapeutic application. This review discusses VDR conformations and their selective stabilization by 1alpha,25(OH)(2)D(3) and its analogues, such as EB1089 and Gemini, as a monomer in solution or as a heterodimer with RXR bound to different VDREs and complexed with coactivator or corepressor proteins. |
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