Structural highlights
Function
[VDR_RAT] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.[1] [MED1_XENTR] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The X-ray crystal structures of the rat VDR ligand-binding domain complexed with 19-norvitamin D compounds that contain an adamantyl substituent at the side-chain terminus, 2a (ADTT), 2b (ADNY), and 2c (ADMI4) and a coactivator peptide derived from DRIP205 are reported. These compounds show a series of partial agonistic (10-75% efficacy)/antagonistic activities. All of these complexed receptors are crystallized in the canonical active conformation, regardless of their activity profiles. The bulky adamantyl side chain does not crowd helix 12 but protrudes into the gap formed by helix 11, loop 11-12, helix 3, and loop 6-7, thereby widening the ligand binding pocket. We suggest that these structural changes destabilize the active protein conformation and reduce its contribution to equilibrium among the active and inactive conformations. The coactivator peptide traps the minor active conformation, and the equilibrium shifts to the active conformation. As a result, these ligands show partial agonistic activities.
Crystal Structures of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and Partial Agonism.,Nakabayashi M, Yamada S, Yoshimoto N, Tanaka T, Igarashi M, Ikura T, Ito N, Makishima M, Tokiwa H, Deluca HF, Shimizu M J Med Chem. 2008 Aug 19. PMID:18710208[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Vanhooke JL, Tadi BP, Benning MM, Plum LA, DeLuca HF. New analogs of 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 with conformationally restricted side chains: evaluation of biological activity and structural determination of VDR-bound conformations. Arch Biochem Biophys. 2007 Apr 15;460(2):161-5. Epub 2006 Dec 12. PMID:17227670 doi:10.1016/j.abb.2006.11.029
- ↑ Nakabayashi M, Yamada S, Yoshimoto N, Tanaka T, Igarashi M, Ikura T, Ito N, Makishima M, Tokiwa H, Deluca HF, Shimizu M. Crystal Structures of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and Partial Agonism. J Med Chem. 2008 Aug 19. PMID:18710208 doi:10.1021/jm8004477
