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Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

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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:
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Internal Receptors01:31

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Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
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Types of Receptors: Internal Receptors01:07

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Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
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Cooperative Binding of Transcription Regulators02:13

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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...
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Signal Transduction: Overview01:26

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Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
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The Two-State Receptor Model01:29

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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...
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Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
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Dimerization of nuclear receptors.

Pierre Germain1, William Bourguet

  • 1Inserm U1054, Centre de Biochimie Structurale, Montpellier, France; CNRS UMR5048, Universités Montpellier 1 & 2, Montpellier, France.

Methods in Cell Biology
|October 23, 2013
PubMed
Summary

Nuclear receptors (NRs) are crucial for development and homeostasis. This review explores NR-NR interactions, detailing how these protein partnerships control gene expression through DNA binding, and offers experimental methods for their study.

Keywords:
DimerizationHeterodimerHomodimerNuclear receptorProtein–protein interactionProtein–protein interface

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Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Genetics

Background:

  • Multicellular organisms rely on intercellular communication for development and function.
  • Nuclear Receptors (NRs) are intracellular transcription factors activated by small signaling molecules.
  • NRs regulate critical biological processes including development, homeostasis, immunity, and reproduction.

Purpose of the Study:

  • To review the current understanding of Nuclear Receptor-Nuclear Receptor (NR-NR) interactions.
  • To highlight the importance of NR-NR interactions in gene regulation.
  • To present experimental protocols for studying NR-NR interactions.

Main Methods:

  • Review of structural and functional studies on NR-NR interactions.
  • Analysis of protein-protein contacts in NR dimerization.
  • Description of experimental approaches for studying NR-NR interactions.

Main Results:

  • NRs function as ligand-inducible transcription factors, often binding DNA as homo- or heterodimers.
  • Combinatorial NR interactions rely on protein contacts that recognize specific DNA response element geometries.
  • These interactions allow for diverse binding sites and physiological specificity.

Conclusions:

  • NR-NR interactions are fundamental to the precise regulation of gene expression.
  • Understanding these interactions is key to deciphering complex biological phenomena.
  • The presented experimental protocols facilitate further investigation into NR-NR interactions.