7QPP

High resolution structure of human VDR ligand binding domain in complex with calcitriol

Summary for 7QPP

• Entry DOI: 10.2210/pdb7qpp/pdb
• Descriptor: Vitamin D3 receptor, 5-{2-[1-(5-HYDROXY-1,5-DIMETHYL-HEXYL)-7A-METHYL-OCTAHYDRO-INDEN-4-YLIDENE]-ETHYLIDENE}-4-METHYLENE-CYCLOHEXANE-1,3-DIOL, SULFATE ION, ... (4 entities in total)
• Functional Keywords: vdr, calcitriol, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 30318.04

Authors

Rochel, N. (deposition date: 2022-01-05, release date: 2022-12-28, Last modification date: 2024-01-31)

Primary citation

Sigueiro, R.,Bianchetti, L.,Peluso-Iltis, C.,Chalhoub, S.,Dejaegere, A.,Osz, J.,Rochel, N.
Advances in Vitamin D Receptor Function and Evolution Based on the 3D Structure of the Lamprey Ligand-Binding Domain.
J.Med.Chem., 65:5821-5829, 2022

PubMed Abstract: 1α,25-dihydroxyvitamin D3 (1,25D) 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 (LBD) complex from the basal vertebrate, sea lamprey (lVDR). Comparison of three-dimensional crystal structures of the lVDR-1,25D complex with higher vertebrate VDR-1,25D structures suggests that 1,25D binds to lVDR similarly to human VDR, 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. Furthermore, residue co-evolution analysis of VDR across vertebrates identifies amino acid positions in H9 and the large insertion domain VDR LBD specific as correlated.

PubMed: 35302785
DOI: 10.1021/acs.jmedchem.2c00171

Experimental method

X-RAY DIFFRACTION (1.52 Å)