Related Experiment Video
Updated: Feb 23, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Synergistic Regulation of Coregulator/Nuclear Receptor Interaction by Ligand and DNA
Ian Mitchelle S de Vera1, Jie Zheng2, Scott Novick2
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA; Department of Molecular Medicine, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.
Abstract:
Nuclear receptor (NR) transcription factors bind various coreceptors, small-molecule ligands, DNA response element sequences, and transcriptional coregulator proteins to affect gene transcription. Small-molecule ligands and DNA are known to influence receptor structure, coregulator protein interaction, and function; however, little is known on the mechanism of synergy between ligand and DNA. Using quantitative biochemical, biophysical, and solution structural methods, including 13C-detected nuclear magnetic resonance and hydrogen/deuterium exchange (HDX) mass spectrometry, we show that ligand and DNA cooperatively recruit the intrinsically disordered steroid receptor coactivator-2 (SRC-2/TIF2/GRIP1/NCoA-2) receptor interaction domain to peroxisome proliferator-activated receptor gamma-retinoid X receptor alpha (PPARγ-RXRα) heterodimer and reveal the binding determinants of the complex. Our data reveal a thermodynamic mechanism by which DNA binding propagates a conformational change in PPARγ-RXRα, stabilizes the receptor ligand binding domain dimer interface, and impacts ligand potency and cooperativity in NR coactivator recruitment.
Related Concept Videos
Co-activators and Co-repressors
Co-activators and Co-repressors
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Cooperative Binding of Transcription Regulators
Cooperative Binding of Transcription Regulators
Signal Transduction: Overview
Typically, signal transduction involves three...

