Structural aspects of Vitamin D endocrinology.
Fiche publication
Date publication
septembre 2017
Journal
Molecular and cellular endocrinology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROCHEL-GUIBERTEAU Natacha
Tous les auteurs :
Rochel N, Molnár F
Lien Pubmed
Résumé
1α,25-Dihydroxvitamin D (1,25(OH)D) is the hormonally active form of vitamin D. 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)D 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 D, 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 D and metabolites by CYP proteins and DBP as well as the structural basis of VDR activation by 1,25(OH)D and metabolites. Additionally, we will describe, the implications of the VDR mutants associated with hereditary vitamin D-resistant rickets (HVDRR) that display impaired function.
Mots clés
Allosteric Regulation, Cholecalciferol, chemistry, Cholestanetriol 26-Monooxygenase, chemistry, Cytochrome P450 Family 2, chemistry, Gene Expression Regulation, Humans, Models, Molecular, Mutation, Receptors, Calcitriol, chemistry, Rickets, Hypophosphatemic, genetics, Vitamin D-Binding Protein, chemistry, Vitamin D3 24-Hydroxylase, chemistry
Référence
Mol. Cell. Endocrinol.. 2017 09 15;453:22-35