Related Experiment Video

Updated: Jun 27, 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

The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1

Elena P Sablin1, April Woods, Irina N Krylova

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 19, 2008
PubMed

Insights

The Dax-1 protein, a nuclear receptor, binds liver receptor homolog 1 (LRH-1) via a novel repressor helix. This interaction explains Dax-1

Area of Science:

  • Molecular biology
  • Structural biology
  • Endocrinology

Background:

  • Dax-1 is a nuclear receptor lacking DNA binding but acting as a corepressor.
  • Its precise mechanism of action and interaction with target receptors remain incompletely understood.

Purpose of the Study:

  • To elucidate the structural basis of Dax-1 interaction with its target, liver receptor homolog 1 (LRH-1).
  • To understand the molecular mechanism underlying Dax-1's potent transcriptional repressor function.

Main Methods:

  • X-ray crystallography to determine the structure of the Dax-1:LRH-1 complex.
  • Site-directed mutagenesis to investigate the role of the repressor helix.

Main Results:

  • The study reveals the crystal structure of Dax-1 bound to LRH-1.
  • A novel repressor helix, derived from the conserved PCFXXLP motif, mediates Dax-1 binding to LRH-1.
  • Mutations in this repressor helix disrupt complex formation and impair Dax-1 function.

Conclusions:

  • The structure provides a molecular explanation for Dax-1's potent corepressor activity.
  • The identified repressor helix and its associated motif are critical for Dax-1 function.
  • Understanding this interaction is crucial for deciphering Dax-1's role in endocrine regulation and associated disorders.

More Related Videos

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation09:07

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

Published on: June 21, 2016

Related Concept Videos

Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...