Related Experiment Video

Updated: Jul 4, 2025

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

Published on: June 21, 2016

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Structural characterization of the DNA binding mechanism of retinoic acid-related orphan receptor gamma

Longying Jiang1, Xueke Liu1, Xujun Liang1

  • 1Department of Pathology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Department of Oncology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Structure (London, England : 1993)
|February 3, 2024
PubMed

Insights

Retinoic acid-related orphan receptor gamma 1 (RORγ1) binds DNA as a homodimer, utilizing its C-terminal extension for recognition and dimerization. This reveals RORγ1

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Genetics

Background:

  • Retinoic acid-related orphan receptor gamma (RORγ) is crucial for biological processes.
  • RORγ's role in immune disorders and cancers is established, but its DNA binding mechanism is unknown.
  • Understanding RORγ DNA binding is key to elucidating its functions.

Purpose of the Study:

  • To elucidate the DNA binding mechanism of Retinoic acid-related orphan receptor gamma 1 (RORγ1).
  • To determine the structural basis of RORγ1's interaction with direct repeat DNA element DR2.

Main Methods:

  • X-ray crystallography was used to determine the structure of the RORγ1 DNA-binding domain (RORγ1-DBD) complexed with DR2 DNA at 2.3 Å resolution.
  • Biochemical assays were employed to investigate the role of the C-terminal extension (CTE) in DNA binding and dimerization.
  • Comparative analysis of DNA binding modes for related nuclear receptors.

Main Results:

  • The crystal structure reveals that RORγ1-DBD forms a homodimer to bind the DR2 DNA motif.
  • The C-terminal extension (CTE) of RORγ1-DBD is essential for both DNA recognition and the formation of the homodimeric interface.
  • Other nuclear receptors like REV-ERB-DBD and RXR-DBD also bind DR2 as homodimers, while NR4A2-DBD binds as a monomer.

Conclusions:

  • A novel DNA binding mechanism for RORγ1 to the DR2 site has been uncovered.
  • The study provides structural insights into RORγ1's homodimeric DNA binding, mediated by its CTE.
  • Findings offer a foundation for understanding RORγ1's biological roles and those of the RORs subfamily.

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