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Updated: Jul 2, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Nuclear receptor interdomain communication is mediated by the hinge with ligand specificity
Saurov Hazarika1, Tracy Yu2, Arumay Biswas1
1Department of Chemistry, Pennsylvania State University, University Park, PA, 16802, USA.
Ligand binding to nuclear receptors like farnesoid X receptor (FXR) causes domain rearrangement. Computational modeling and assays reveal the hinge region is crucial for this interdomain communication.
Area of Science:
- Molecular Biology
- Structural Biology
- Computational Biology
Background:
- Nuclear receptors are transcription factors regulated by ligand binding.
- Interdomain communication in full-length nuclear receptors remains poorly understood due to experimental challenges.
Approach:
- Computational modeling and molecular dynamics simulations (>10 microseconds) were used to study the full-length farnesoid X receptor (FXR).
- Enhanced sampling simulations and protein-protein interaction assays provided experimental validation.
Key Points:
- Ligand binding induces selective domain rearrangement and interdomain contact in FXR.
- The flexible hinge region plays a critical role in mediating these interdomain interactions.
- This study provides insights into the allosteric regulation of nuclear receptors.
Conclusions:
- The findings illuminate novel aspects of interdomain communication in the farnesoid X receptor.
- A framework is established for characterizing the structure and dynamics of other full-length nuclear receptors.
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