1FM6

THE 2.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF THE HETERODIMER OF THE HUMAN RXRALPHA AND PPARGAMMA LIGAND BINDING DOMAINS RESPECTIVELY BOUND WITH 9-CIS RETINOIC ACID AND ROSIGLITAZONE AND CO-ACTIVATOR PEPTIDES.

1FM6 の概要

• エントリーDOI: 10.2210/pdb1fm6/pdb
• 関連するPDBエントリー: 1FM9
• 分子名称: RETINOIC ACID RECEPTOR RXR-ALPHA, PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA, STEROID RECEPTOR COACTIVATOR, ... (6 entities in total)
• 機能のキーワード: the heterodimer of the nuclear receptor ligand binding domains of rxralpha and ppargamma bound respectively with 9-cis retinoic acid and rosiglitazone and co-activator peptides, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : P19793 P37231
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 128064.36

構造登録者

Gampe Jr., R.T.,Montana, V.G.,Lambert, M.H.,Miller, A.B.,Bledsoe, R.K.,Milburn, M.V.,Kliewer, S.A.,Willson, T.M.,Xu, H.E. (登録日: 2000-08-16, 公開日: 2001-02-16, 最終更新日: 2024-02-07)

主引用文献

Gampe Jr., R.T.,Montana, V.G.,Lambert, M.H.,Miller, A.B.,Bledsoe, R.K.,Milburn, M.V.,Kliewer, S.A.,Willson, T.M.,Xu, H.E.
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
Mol.Cell, 5:545-555, 2000

PubMed Abstract: The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazolidinediones (TZDs). We report the crystal structures of the PPARgamma and RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides. The PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha. The heterodimer interface is composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9. The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARgamma/RXRbeta heterodimer by 9cRA.

PubMed: 10882139
DOI: 10.1016/S1097-2765(00)80448-7

実験手法

X-RAY DIFFRACTION (2.1 Å)