Ligand-induced peroxisome proliferator-activated receptor α conformational change

Paul Dowell, Valerie J. Peterson, T. Mark Zabriskie, Mark Leid

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Structurally diverse peroxisome proliferators and related compounds that have been demonstrated to induce the ligand-dependent transcriptional activation function of mouse peroxisome proliferator-activated receptor α (mPPARα) in transfection experiments were tested for the ability to induce conformational changes within mPPARα in vitro. WY-14,643, 5,8,11,14- eicosatetraynoic acid, LY-171883, and clofibric acid all directly induced mPPARα conformational changes as evidenced by a differential protease sensitivity assay. Carboxyl-terminal truncation mutagenesis of mPPARα differentially affected the ability of these ligands to induce conformational changes suggesting that PPAR ligands may make distinct contacts with the receptor. Direct interaction of peroxisome proliferators and related compounds with, and the resulting conformational alteration(s) in, mPPARα may facilitate interaction of the receptor with transcriptional intermediary factors and/or the general transcription machinery and, thus, may underlie the molecular basis of ligand-dependent transcriptional activation mediated by mPPARα.

Original languageEnglish (US)
Pages (from-to)2013-2020
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number3
DOIs
StatePublished - Feb 1 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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