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Updated: Jun 8, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Orphan nuclear receptors: structural mechanisms, ligand discovery, and therapeutic potential

Yunlong Liu1, Shirong Wei1, Ziheng Wang1

  • 1School of Life Sciences, Tiangong University, Tianjin 300387, China.

Cellular Signalling
|June 6, 2026
PubMed

Insights

Orphan nuclear receptors (ONRs) regulate key physiological processes. This review details ONR ligand research, highlighting their roles in metabolism, development, and disease, and discusses strategies for therapeutic targeting.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Structural Biology

Background:

  • Orphan nuclear receptors (ONRs) are crucial nuclear receptor superfamily members lacking defined ligands.
  • They regulate vital functions including metabolism, development, neural activity, and tumorigenesis.
  • Advances in structural and chemical biology enhance understanding of ONR ligand interactions.

Purpose of the Study:

  • To review current progress in ONR ligand research.
  • To categorize ONRs based on physiological roles and disease involvement.
  • To discuss structural insights into ligand recognition and discovery strategies.

Main Methods:

  • Literature review of ONR ligand research.
  • Analysis of structural biology data for ligand-receptor complexes.
  • Categorization of ONRs by physiological function and disease association.
  • Discussion of ligand discovery strategies including co-purification and screening.

Main Results:

  • ONRs are involved in metabolic homeostasis, development, reproduction, neuro-immune regulation, and cancer.
  • Structural studies identified ligands like lipids, heme, and phospholipids for receptors such as ROR, HNF-4, and REV-ERB.
  • Other ONRs like TR4 and DAX-1 show functional evidence for ligand interactions.
  • Ligand discovery employs co-purification, screening, structural, and computational methods.

Conclusions:

  • Understanding ONR ligand interactions is key to elucidating their roles in health and disease.
  • Structural variations in ligand-binding domains influence receptor regulation.
  • Challenges remain in ligand identification and achieving drug selectivity.
  • Integrating multi-omics and structural approaches will advance therapeutic targeting of ONRs.
Keywords:
Ligand discovery strategiesLigand-binding domainOrphan nuclear receptorsStructural mechanismsTherapeutic potential

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