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Related Concept Videos

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...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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 affinity and are together...
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...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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 cells.
Two...
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...
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...

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Related Experiment Video

Updated: Jun 1, 2026

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization
09:19

Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization

Published on: March 16, 2020

Structure-based screening and a conformational biosensor identify a GPR183 inverse agonist and an activation switch.

Louise Andersson1, Michele Roggia2, Kittikorn Wangriatisak3,4

  • 1Molecular Pharmacology of GPCRs, Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.

Nature Communications
|May 30, 2026
PubMed
Summary

Researchers identified compound 78, a potent inverse agonist for GPR183, effectively inhibiting immune cell migration. This discovery offers new therapeutic strategies for inflammatory and autoimmune diseases.

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A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
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Monitoring GPCR-&#946;-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
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Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization
09:19

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Published on: March 16, 2020

A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
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Monitoring GPCR-&#946;-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
08:21

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Published on: June 28, 2019

Area of Science:

  • Pharmacology
  • Immunology
  • Biochemistry

Background:

  • G protein-coupled receptor 183 (GPR183) is a key regulator of immune cell migration.
  • Dysregulation of GPR183 signaling is implicated in inflammatory, autoimmune, and oncological diseases.

Purpose of the Study:

  • To identify novel inverse agonists targeting GPR183.
  • To elucidate the molecular mechanisms of GPR183 activation and signaling.
  • To evaluate the therapeutic potential of identified inhibitors in immune cell migration.

Main Methods:

  • AI-driven virtual screening and biophysical assays for compound identification.
  • Biochemical assays to assess Gi signaling and β-arrestin2 recruitment.
  • Molecular dynamics simulations, mutagenesis, and conformational biosensors for structural analysis.
  • Ex vivo assays using peripheral blood mononuclear cells to evaluate cell migration inhibition.

Main Results:

  • Compound 78 identified as a potent inverse agonist, inhibiting constitutive and agonist-induced Gi signaling and β-arrestin2 recruitment.
  • Structural studies confirmed compound 78 binds within the GPR183 receptor core.
  • Compound 78 effectively blocked agonist-driven migration of peripheral blood mononuclear cells ex vivo.
  • Tyrosine 260 (Y2606.51) in transmembrane helix 6 identified as critical for GPR183 activation and compound 78 efficacy, revealing a switch mechanism.

Conclusions:

  • Compound 78 represents a potent chemical scaffold for GPR183 inhibition.
  • Understanding GPR183 activation mechanisms provides insights into receptor function.
  • This study offers novel tools and therapeutic strategies for targeting GPR183 in various diseases.