4RUJ

Crystal structure of zVDR L337H mutant-VD complex

Summary for 4RUJ

• Entry DOI: 10.2210/pdb4ruj/pdb
• Related: 2HC4 2HCD 4RUO 4RUP
• Descriptor: Vitamin D3 receptor A, Nuclear receptor coactivator 1, 5-{2-[1-(5-HYDROXY-1,5-DIMETHYL-HEXYL)-7A-METHYL-OCTAHYDRO-INDEN-4-YLIDENE]-ETHYLIDENE}-4-METHYLENE-CYCLOHEXANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: alpha helical sandwich, transcription factor, retinoid x receptor, ligand, dna, phosphorylation, nucleus, transcription factor-transcription regulator complex, transcription factor/transcription regulator
• Biological source: Danio rerio (leopard danio,zebra danio,zebra fish); More
• Total number of polymer chains: 2
• Total formula weight: 36278.37

Authors

Huet, T.,Moras, D.,Rochel, N. (deposition date: 2014-11-20, release date: 2015-10-07, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.352 Å)