2NXX

Crystal Structure of the Ligand-Binding Domains of the T.castaneum (Coleoptera) Heterodimer EcrUSP Bound to Ponasterone A

2NXX の概要

• エントリーDOI: 10.2210/pdb2nxx/pdb
• 分子名称: Ultraspiracle (USP, NR2B4), Ecdysone Receptor (EcR, NRH1), 2,3,14,20,22-PENTAHYDROXYCHOLEST-7-EN-6-ONE, ... (4 entities in total)
• 機能のキーワード: hormone receptor, apo and holo ligand binding pocket, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Tribolium castaneum (red flour beetle); 詳細
• 細胞内の位置: Nucleus : A1JUG2 A1JUG3
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 223683.36

構造登録者

Iwema, T.,Billas, I.,Moras, D. (登録日: 2006-11-20, 公開日: 2007-10-02, 最終更新日: 2024-04-03)

主引用文献

Iwema, T.,Billas, I.M.,Beck, Y.,Bonneton, F.,Nierengarten, H.,Chaumot, A.,Richards, G.,Laudet, V.,Moras, D.
Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor.
Embo J., 26:3770-3782, 2007

PubMed Abstract: Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as ubiquitous heterodimerization partners of many nuclear receptors. While it has long been accepted that a wide range of ligands can activate vertebrate/mollusc RXRs, the existence and necessity of specific endogenous ligands activating RXR-USP in vivo is still matter of intense debate. Here we report the existence of a novel type of RXR-USP with a ligand-independent functional conformation. Our studies involved Tribolium USP (TcUSP) as representative of most arthropod RXR-USPs, with high sequence homology to vertebrate/mollusc RXRs. The crystal structure of the ligand-binding domain of TcUSP was solved in the context of the functional heterodimer with the ecdysone receptor (EcR). While EcR exhibits a canonical ligand-bound conformation, USP adopts an original apo structure. Our functional data demonstrate that TcUSP is a constitutively silent partner of EcR, and that none of the RXR ligands can bind and activate TcUSP. These findings together with a phylogenetic analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics.

PubMed: 17673910
DOI: 10.1038/sj.emboj.7601810

実験手法

X-RAY DIFFRACTION (2.75 Å)