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Mol Cell Endocrinol. 2017 Sep 15;453:22-35. doi: 10.1016/j.mce.2017.02.046. Epub 2017 Feb 28.

Structural aspects of Vitamin D endocrinology.

Author information

1
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de La Santé et de La Recherche Médicale (INSERM), U964/Centre National de Recherche Scientifique (CNRS), UMR7104/Université de Strasbourg, 67404 Illkirch, France. Electronic address: rochel@igbmc.fr.
2
Institute of Biopharmacy, School of Pharmacy, Faculty of Heath Science, University of Eastern Finland, Yliopistonranta 1C, Canthia 2036, 70210 Kuopio, Finland. Electronic address: ferdinandmolnar@gmail.com.

Abstract

1α,25-Dihydroxvitamin D3 (1,25(OH)2D3) is the hormonally active form of vitamin D3. Its synthesis and its metabolites, their transport and elimination as well as action on transcriptional regulation involves the harmonic cooperation of diverse proteins with vitamin D binding capacities such as vitamin D binding protein (DBP), cytochrome P450 enzymes or the nuclear vitamin receptor (VDR). The genomic mechanism of 1,25(OH)2D3 action involves its binding to VDR that functionally acts as a heterodimer with retinoid X receptor. The crystal structures of the most important proteins for vitamin D3, VDR, DBP, CYP2R1 and CYP24A1, have provided identification of mechanisms of actions of these proteins and those mediating VDR-regulated transcription. This review will present the structural information on recognition of the vitamin D3 and metabolites by CYP proteins and DBP as well as the structural basis of VDR activation by 1,25(OH)2D3 and metabolites. Additionally, we will describe, the implications of the VDR mutants associated with hereditary vitamin D-resistant rickets (HVDRR) that display impaired function.

KEYWORDS:

Allostery; CYPs; DBP; HVDRR; Structure; VDR; Vitamin D3

PMID:
28257826
DOI:
10.1016/j.mce.2017.02.046
[Indexed for MEDLINE]

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