1YNW

Crystal Structure of Vitamin D Receptor and 9-cis Retinoic Acid Receptor DNA-Binding Domains Bound to a DR3 Response Element

1YNW の概要

• エントリーDOI: 10.2210/pdb1ynw/pdb
• 分子名称: 5'-d(*TP*TP*AP*GP*GP*TP*CP*AP*CP*GP*AP*AP*GP*GP*TP*CP*AP*A)-3', 5'-d(*TP*TP*TP*GP*AP*CP*CP*TP*TP*CP*GP*TP*GP*AP*CP*CP*TP*A)-3', Vitamin D3 Receptor, ... (5 entities in total)
• 機能のキーワード: vdr; rxr; nuclear receptor; protein-dna complex, transcription-dna complex, transcription/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P11473 P19793
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 35710.13

構造登録者

Shaffer, P.L.,Gewirth, D.T. (登録日: 2005-01-25, 公開日: 2005-02-15, 最終更新日: 2023-08-23)

主引用文献

Shaffer, P.L.,Gewirth, D.T.
Structural analysis of RXR-VDR interactions on DR3 DNA
J.Steroid Biochem.Mol.Biol., 89-90:215-219, 2004

PubMed Abstract: The Vitamin D receptor (VDR) is a ligand-responsive transcription factor that forms homo- or heterodimers on response elements composed of two hexameric half-sites separated by three base pairs of spacer DNA. Binding of 1alpha,25-dihydroxyvitamin D(3) to the full-length VDR causes destabilization of the VDR homodimer and formation of a heterodimeric complex with the 9-cis retinoic acid receptor (RXR). VDR and RXR DNA-binding domains (DBDs) do not mimic this behavior, however: VDR DBD homodimers are formed exclusively, even in the presence of excess RXR DBD. Exploiting the asymmetry of the heterodimer and our knowledge of the homodimeric DBD interface, we have engineered VDR mutants that disfavor the homodimeric complex and allow for the formation of heterodimeric DBD complexes with RXR on DR3 elements. One of these complexes has been crystallized and its structure determined. However, the polarity of the proteins relative to the DNA is non-physiological due to crystal packing between symmetry-related VDR DBD protomers. This reveals a flattened energy landscape that appears to rely on elements outside of the core DBD for response element discrimination in the heterodimer.

PubMed: 15225774
DOI: 10.1016/j.jsbmb.2004.03.084

実験手法

X-RAY DIFFRACTION (3 Å)