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Both Coactivator LXXLL Motif-dependent and -independent Interactions Are Required for Peroxisome Proliferator-activated Receptor γ (PPARγ) Function
- Source :
- Journal of Biological Chemistry. 275:3733-3736
- Publication Year :
- 2000
- Publisher :
- Elsevier BV, 2000.
-
Abstract
- Nuclear receptor activation is dependent on recruitment of coactivators, including CREB-binding protein (CBP/p300) and steroid receptor coactivator-1 (SRC-1). A three-dimensional NMR approach was used to probe the coactivator binding interface in the peroxisome proliferator-activated receptor gamma (PPARgamma) ligand binding domain (LBD). In the presence of a CBP peptide, peaks corresponding to 20 residues in helices 3, 4, 5, and 12 of the LBD were attenuated. Alanine mutants revealed that K301A, V315A, Y320A, L468A, and E471A were required for binding of both CBP and SRC-1 and for cell-based transcription. Several additional amino acids in helix 4 of the PPARgammaLBD were defective with respect to CBP recruitment, but retained relatively normal SRC-1 recruitment. Thus these amino acid residues may be important determinants of specificity for nuclear receptor LBD interactions with discrete coactivator molecules.
- Subjects :
- Models, Molecular
Transcriptional Activation
Peroxisome proliferator-activated receptor gamma
Magnetic Resonance Spectroscopy
Receptors, Cytoplasmic and Nuclear
Peroxisome proliferator-activated receptor
Biochemistry
Protein Structure, Secondary
Nuclear Receptor Coactivator 1
Coactivator
Animals
Humans
Molecular Biology
Histone Acetyltransferases
chemistry.chemical_classification
Binding Sites
Nuclear Proteins
Cell Biology
Cell biology
Nuclear receptor coactivator 1
chemistry
Nuclear receptor
COS Cells
Mutation
Nuclear receptor coactivator 3
Trans-Activators
Nuclear receptor coactivator 2
PPARGC1B
Protein Binding
Transcription Factors
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 275
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....b5417339655837d55be4b67bb0ac63ea