Advances in vitamin D receptor function and evolution based on the 3D structure of the lamprey ligand binding domain - Archive ouverte HAL Access content directly
Journal Articles Journal of Medicinal Chemistry Year : 2022

Advances in vitamin D receptor function and evolution based on the 3D structure of the lamprey ligand binding domain

Abstract

1α,25-dihydroxyvitamin D 3 (1,25D 3) regulates many physiological processes in vertebrates by binding to the Vitamin D Receptor (VDR). Phylogenetic analysis indicates that jawless fishes are the most basal vertebrates exhibiting a VDR gene. To elucidate the mechanism driving VDR activation during evolution, we determined the crystal structure of the VDR ligand binding domain complex from the basal vertebrate Petromyzon marinus, sea lamprey (lVDR). Comparison of 3D crystal structure of lVDR-1,25D 3 complex with higher vertebrates VDR-1,25D 3 structures suggest that 1,25D 3 binds to lVDR similarly to human VDR (hVDR), but with unique features for lVDR around linker regions between H11 and H12 and between H9 and H10. These structural differences may contribute to the marked species differences in transcriptional responses. Further, residue co-evolution analysis among vertebrates VDR identifies amino-acid positions in H9 and the large insertion domain (iD) VDR LBD specific.
Fichier principal
Vignette du fichier
lVDR_JMC2022.pdf (1.42 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03745351 , version 1 (04-08-2022)

Identifiers

Cite

Rita Sigüeiro, Laurent Bianchetti, Carole Peluso-Iltis, Sandra Chalhoub, Annick Dejaegere, et al.. Advances in vitamin D receptor function and evolution based on the 3D structure of the lamprey ligand binding domain. Journal of Medicinal Chemistry, 2022, 65 (7), pp.5821-5829. ⟨10.1021/acs.jmedchem.2c00171⟩. ⟨hal-03745351⟩
87 View
69 Download

Altmetric

Share

Gmail Facebook X LinkedIn More