Related Experiment Video

Updated: Jan 23, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
09:07

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

Published on: June 21, 2016

8.6K

Interplay of Protein Disorder in Retinoic Acid Receptor Heterodimer and Its Corepressor Regulates Gene Expression

Tiago N Cordeiro1, Nathalie Sibille2, Pierre Germain2

  • 1Centre de Biochimie Structurale (CBS). CNRS, INSERM, Université de Montpellier, 29, rue de Navacelles, 34090 Montpellier, France; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, 2790-157 Oeiras, Portugal.

Structure (London, England : 1993)
|June 11, 2019
PubMed

Insights

Retinoic acid receptor (RAR) activity relies on intrinsic disorder and dynamic structural changes. Ligand binding and receptor mutations tune the balance between repression and activation by modulating corepressor complexes.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biophysics

Background:

  • Retinoic acid receptor (RAR) forms heterodimers with retinoid X receptor (RXR).
  • This complex recruits transcriptional corepressors, leading to gene repression.
  • Understanding RAR regulation is crucial for various biological processes.

Purpose of the Study:

  • To investigate the role of intrinsic disorder in RAR/RXR transcriptional regulation.
  • To elucidate the mechanism of corepressor N-CoR interaction with RAR/RXR.
  • To understand how ligands and mutations affect RAR/RXR activity.

Main Methods:

  • Integration of structural, biophysical, and computational data.
  • Analysis of the dynamics of RAR and RXR H12 regions.
  • Characterization of N-CoR structure and its interactions.

Main Results:

  • Intrinsic disorder is essential for precise RAR activity regulation.
  • Structural dynamics of RAR/RXR H12 regions are key regulatory mechanisms.
  • N-CoR, though largely disordered, has conserved structured regions enabling transient contacts.
  • N-CoR forms a multivalent, cooperative complex with RAR/RXR, existing in an equilibrium of conformational states.
  • This equilibrium is tunable by ligands and receptor mutations, balancing repression and activation.

Conclusions:

  • Intrinsic disorder and conformational dynamics are fundamental to RAR/RXR function.
  • The N-CoR complex's equilibrium is a critical regulatory hub for gene transcription.
  • Targeting this equilibrium offers potential therapeutic strategies for diseases involving RAR signaling.
Keywords:
Nuclear Magnetic Resonancecorepressordynamic protein complexintegrative structural biologyintrinsically disordered proteinmultivalent proteinretinoic acid receptorsmall-angle X-ray scatteringstructural modelingtranscriptional regulation

More Related Videos

Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion06:54

Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion

Published on: June 15, 2019

6.4K
Author Spotlight: An Optimized Automated Method for Investigating Retinoic Acid Receptors in Neuronal Mitochondria08:33

Author Spotlight: An Optimized Automated Method for Investigating Retinoic Acid Receptors in Neuronal Mitochondria

Published on: July 28, 2023

972

Related Concept Videos

What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
195.1K
Constitutive and Regulated Gene Expression01:27

Constitutive and Regulated Gene Expression

Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
986
Intrinsically Disordered Proteins02:18

Intrinsically Disordered Proteins

Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
19.3K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
8.8K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
25.8K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.3K