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Related Concept Videos

G-protein Coupled Receptors01:21

G-protein Coupled Receptors

131.6K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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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...
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Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

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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,...
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Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

7.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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GPCR Desensitization01:12

GPCR Desensitization

7.9K
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...
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Related Experiment Video

Updated: Jan 17, 2026

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
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Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

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Activation primes GPCRs for versatile coupling.

Vsevolod V Gurevich1, Eugenia V Gurevich1

  • 1Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.

Cell Chemical Biology
|September 19, 2025
PubMed
Summary
This summary is machine-generated.

G protein-coupled receptors (GPCRs) undergo activation via agonist-induced disorder. This cytoplasmic disorder is key for versatile coupling with G proteins, kinases, and arrestins, explaining GPCR activation mechanisms.

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Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

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Last Updated: Jan 17, 2026

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
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Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • G protein-coupled receptors (GPCRs) are crucial cell surface receptors involved in numerous physiological processes.
  • GPCR activation leads to interactions with intracellular proteins like G proteins, GPCR kinases, and arrestins.

Purpose of the Study:

  • To elucidate the molecular basis of GPCR activation.
  • To understand how agonist binding triggers versatile downstream signaling.

Main Methods:

  • The study by Guo et al. utilized advanced biophysical and biochemical techniques.
  • Investigated the conformational changes on the cytoplasmic side of GPCRs upon agonist stimulation.

Main Results:

  • Demonstrated that agonist binding induces a disordered state on the cytoplasmic side of GPCRs.
  • This agonist-induced disorder facilitates efficient and versatile coupling with multiple effector proteins.

Conclusions:

  • The findings reveal a novel mechanism for GPCR activation, emphasizing the role of conformational disorder.
  • This molecular understanding of GPCR activation is vital for developing targeted therapeutics.