Related Experiment Video

Updated: Jul 18, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs

Stéphanie Gaillard1, Linda L Grasfeder1, Christiane L Haeffele1

  • 1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710.

Molecular Cell
|December 13, 2006
PubMed

Insights

Researchers developed a method to study orphan nuclear receptors (ONRs) by isolating specific receptor-cofactor pairs. This technique allows for the precise definition of biological responses linked to these complexes, advancing our understanding of ONR functions.

Area of Science:

  • Molecular biology
  • Genetics
  • Biochemistry

Background:

  • Orphan nuclear receptors (ONRs) present challenges in defining target genes and biological responses due to the lack of specific agonists and antagonists.
  • Many ONRs are regulated by interacting cofactors rather than classical small molecules, necessitating novel approaches to study their function.

Purpose of the Study:

  • To develop and apply a genetic method for isolating specific receptor-cofactor pairs in cells.
  • To define the biological responses attributable to individual ONR-cofactor complexes.
  • To investigate the biology of estrogen-related receptor alpha (ERRalpha) using this novel approach.

Main Methods:

  • Utilized combinatorial peptide phage display to engineer cofactor-interacting domains.
  • Customized the receptor interacting domain of PGC-1alpha for selective interaction with a target nuclear receptor.
  • Applied the engineered cofactor to study ERRalpha in cultured liver cells.

Main Results:

  • Successfully engineered a selective interaction between a modified cofactor and a specific nuclear receptor.
  • Demonstrated the ability to genetically isolate and study specific ONR-cofactor pairs.
  • Provided insights into the biological roles of ERRalpha in liver cells through this targeted approach.

Conclusions:

  • The developed method enables the precise dissection of ONR-cofactor complex functions.
  • This approach overcomes limitations posed by the absence of specific pharmacological modulators for ONRs.
  • The study highlights the potential of genetically engineered cofactors for advancing nuclear receptor research.

More Related Videos

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation12:09

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

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...
The Two-State Receptor Model01:29

The Two-State Receptor Model

The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...
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:
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...