4ZO1

Crystal Structure of the T3-bound TR-beta Ligand-binding Domain in complex with RXR-alpha

4ZO1 の概要

• エントリーDOI: 10.2210/pdb4zo1/pdb
• 分子名称: Thyroid hormone receptor beta, Nuclear receptor coactivator 2, Retinoic acid receptor RXR-alpha, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, transcription factor, ligand binding, protein-ligand complex, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: P10828 P19793
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 55562.81

構造登録者

Bruning, J.B.,Kojetin, D.J.,Matta-Camacho, E.,Hughes, T.S.,Srinivasan, S.,Nwachukwu, J.C.,Cavett, V.,Nowak, J.,Chalmers, M.J.,Marciano, D.P.,Kamenecka, T.M.,Rance, M.,Shulman, A.I.,Mangelsdorf, D.J.,Griffin, P.R.,Nettles, K.W. (登録日: 2015-05-05, 公開日: 2015-09-02, 最終更新日: 2023-11-15)

主引用文献

Kojetin, D.J.,Matta-Camacho, E.,Hughes, T.S.,Srinivasan, S.,Nwachukwu, J.C.,Cavett, V.,Nowak, J.,Chalmers, M.J.,Marciano, D.P.,Kamenecka, T.M.,Shulman, A.I.,Rance, M.,Griffin, P.R.,Bruning, J.B.,Nettles, K.W.
Structural mechanism for signal transduction in RXR nuclear receptor heterodimers.
Nat Commun, 6:8013-8013, 2015

PubMed Abstract: A subset of nuclear receptors (NRs) function as obligate heterodimers with retinoid X receptor (RXR), allowing integration of ligand-dependent signals across the dimer interface via an unknown structural mechanism. Using nuclear magnetic resonance (NMR) spectroscopy, x-ray crystallography and hydrogen/deuterium exchange (HDX) mass spectrometry, here we show an allosteric mechanism through which RXR co-operates with a permissive dimer partner, peroxisome proliferator-activated receptor (PPAR)-γ, while rendered generally unresponsive by a non-permissive dimer partner, thyroid hormone (TR) receptor. Amino acid residues that mediate this allosteric mechanism comprise an evolutionarily conserved network discovered by statistical coupling analysis (SCA). This SCA network acts as a signalling rheostat to integrate signals between dimer partners, ligands and coregulator-binding sites, thereby affecting signal transmission in RXR heterodimers. These findings define rules guiding how NRs integrate two ligand-dependent signalling pathways into RXR heterodimer-specific responses.

PubMed: 26289479
DOI: 10.1038/ncomms9013

実験手法

X-RAY DIFFRACTION (3.221 Å)