4RUP

Crystal structure of zVDR L337H mutant-Gemini72 complex

4RUP の概要

• エントリーDOI: 10.2210/pdb4rup/pdb
• 関連するPDBエントリー: 2HC4 2HCD 4RUJ 4RUO
• 分子名称: Vitamin D3 receptor A, Nuclear receptor coactivator 1, (1R,3R,7E,17beta)-17-[(1R)-6,6,6-trifluoro-5-hydroxy-1-(4-hydroxy-4-methylpentyl)-5-(trifluoromethyl)hex-3-yn-1-yl]-9,1 0-secoestra-5,7-diene-1,3-diol, ... (4 entities in total)
• 機能のキーワード: alpha helical sandwich, transcription factor, retinoid x receptor, ligand, dna, phosphorylation, nucleus
• 由来する生物種: Danio rerio (leopard danio,zebra danio,zebra fish); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36456.40

構造登録者

Huet, T.,Moras, D.,Rochel, N. (登録日: 2014-11-21, 公開日: 2015-10-07, 最終更新日: 2024-02-28)

主引用文献

Huet, T.,Laverny, G.,Ciesielski, F.,Molnar, F.,Ramamoorthy, T.G.,Belorusova, A.Y.,Antony, P.,Potier, N.,Metzger, D.,Moras, D.,Rochel, N.
A vitamin D receptor selectively activated by gemini analogs reveals ligand dependent and independent effects.
Cell Rep, 10:516-526, 2015

PubMed Abstract: The bioactive form of vitamin D [1,25(OH)2D3] regulates mineral and bone homeostasis and exerts potent anti-inflammatory and antiproliferative properties through binding to the vitamin D receptor (VDR). The 3D structures of the VDR ligand-binding domain with 1,25(OH)2D3 or gemini analogs unveiled the molecular mechanism underlying ligand recognition. On the basis of structure-function correlations, we generated a point-mutated VDR (VDR(gem)) that is unresponsive to 1,25(OH)2D3, but the activity of which is efficiently induced by the gemini ligands. Moreover, we show that many VDR target genes are repressed by unliganded VDR(gem) and that mineral ion and bone homeostasis are more impaired in VDR(gem) mice than in VDR null mice, demonstrating that mutations abolishing VDR ligand binding result in more severe skeletal defects than VDR null mutations. As gemini ligands induce VDR(gem) transcriptional activity in mice and normalize their serum calcium levels, VDR(gem) is a powerful tool to further unravel both liganded and unliganded VDR signaling.

PubMed: 25620699
DOI: 10.1016/j.celrep.2014.12.045

実験手法

X-RAY DIFFRACTION (2.75 Å)