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Related Concept Videos

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:
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...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...

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Related Experiment Video

Updated: May 15, 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

Solution Structures of PPARγ2/RXRα Complexes.

Judit Osz1, Maxim V Pethoukhov, Serena Sirigu

  • 1Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de Recherche Scientifique (CNRS) UMR 7104, Institut National de Santé et de Recherche Médicale (INSERM) U964, Université de Strasbourg, 67404 Illkirch, France.

PPAR Research
|January 16, 2013
PubMed
Summary

Peroxisome proliferator-activated receptor gamma (PPARγ) and retinoid X receptor (RXR) form a heterodimer crucial for gene regulation. Structural studies reveal DNA binding induces asymmetry, affecting coactivator TIF2 binding.

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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

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Last Updated: May 15, 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

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

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Endocrinology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARγ) is vital for glucose homeostasis and insulin sensitivity.
  • PPARγ requires heterodimerization with retinoid X receptor (RXR) to bind DNA and regulate gene networks.
  • Coactivators like p160 and PGC-1α interact with the PPARγ/RXR complex to modulate gene expression.

Purpose of the Study:

  • To elucidate the structural basis of coactivator recognition by the PPARγ/RXRα heterodimer.
  • To determine the topological organization of PPARγ/RXRα complexes bound to DNA and coactivators.
  • To understand how DNA influences the structure and function of the PPARγ/RXRα heterodimer.

Main Methods:

  • Small-angle X-ray scattering (SAXS) was employed to study the structural properties of the PPARγ/RXRα heterodimer.
  • The study analyzed complexes of PPARγ/RXRα with DNA from a regulated gene and the TIF2 receptor interacting domain (RID).
  • Solution structures were determined to reveal the overall architecture and binding interfaces.

Main Results:

  • The solution structures demonstrated an asymmetrical organization of the PPARγ/RXRα heterodimer.
  • DNA binding was identified as a critical factor in positioning the heterodimer, inducing this asymmetry.
  • Asymmetrical binding of the TIF2 coactivator to the PPARγ/RXRα heterodimer was observed.

Conclusions:

  • DNA plays a crucial role in dictating the structural conformation of the PPARγ/RXRα heterodimer.
  • The observed asymmetry influences the interaction dynamics with coactivators such as TIF2.
  • These findings provide insights into the molecular mechanisms underlying PPARγ-mediated gene regulation.