3CS8

Structural and Biochemical Basis for the Binding Selectivity of PPARg to PGC-1a

3CS8 の概要

• エントリーDOI: 10.2210/pdb3cs8/pdb
• 分子名称: Peroxisome proliferator-activated receptor gamma, PGC-1alfa peptide, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: coactivator, nuclear receptor, alternative splicing, diabetes mellitus, disease mutation, dna-binding, metal-binding, nucleus, obesity, phosphoprotein, polymorphism, transcription, transcription regulation, zinc, zinc-finger, rna-binding, nuclear protein
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Nucleus: P37231 Q9UBK2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33296.64

構造登録者

Li, Y.,Martynowski, D. (登録日: 2008-04-09, 公開日: 2008-06-03, 最終更新日: 2024-02-21)

主引用文献

Li, Y.,Kovach, A.,Suino-Powell, K.,Martynowski, D.,Xu, H.E.
Structural and biochemical basis for the binding selectivity of peroxisome proliferator-activated receptor gamma to PGC-1alpha.
J.Biol.Chem., 283:19132-19139, 2008

PubMed Abstract: The functional interaction between the peroxisome proliferator-activated receptor gamma (PPARgamma) and its coactivator PGC-1alpha is crucial for the normal physiology of PPARgamma and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPARgamma ligand-binding domain bound to rosiglitazone and to a large PGC-1alpha fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1alpha and the PPARgamma coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1alpha is capable of binding to PPARgamma. Our studies reveal that the strong interaction of PGC-1alpha and PPARgamma is mediated through both hydrophobic and specific polar interactions. Mutations within the context of the full-length PGC-1alpha indicate that the first PGC-1alpha motif is necessary and sufficient for PGC-1alpha to coactivate PPARgamma in the presence or absence of rosiglitazone. These results provide a molecular basis for specific recruitment and functional interplay between PPARgamma and PGC-1alpha in glucose homeostasis and adipocyte differentiation.

PubMed: 18469005
DOI: 10.1074/jbc.M802040200

実験手法

X-RAY DIFFRACTION (2.3 Å)