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Related Concept Videos

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

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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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G-protein Coupled Receptors01:21

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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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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.
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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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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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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
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Related Experiment Video

Updated: Jan 7, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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Type-1 Cannabinoid Receptor Promiscuous Coupling: Computational Insights into Receptor-G Protein Interaction

Alessandro Berghella1, Tomasz Maciej Stepniewski2,3, Annalaura Sabatucci1

  • 1Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy.

International Journal of Molecular Sciences
|December 30, 2025
PubMed
Summary

This study reveals the structural basis for how the cannabinoid receptor 1 (CB1) interacts with the Gs protein. This finding advances understanding of CB1 receptor signaling and potential therapeutic development.

Keywords:
CB1 receptorGPCRGs proteinendocannabinoid systemmolecular dynamics

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Area of Science:

  • Molecular pharmacology
  • Structural biology
  • Computational biophysics

Background:

  • Cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) crucial for physiological processes, primarily signaling through Gi proteins.
  • Emerging evidence indicates CB1 can also activate the Gs protein, but the structural mechanisms remain poorly understood.

Purpose of the Study:

  • To computationally elucidate the structural basis of the interaction between the CB1 receptor and the Gs protein.
  • To provide a structural model for CB1-Gs complex formation.

Main Methods:

  • Protein-protein docking simulations were employed to predict the complex structure.
  • Extensive molecular dynamics simulations were performed to refine and validate the model.
  • The generated model was compared against existing experimental data and known GPCR-Gs structures.

Main Results:

  • A valid structural model of the CB1-Gs complex was successfully generated.
  • The model aligns well with current experimental findings and established GPCR-Gs complex structures.
  • The study provides novel insights into the structural determinants of CB1 coupling with different G proteins.

Conclusions:

  • The developed structural model offers a foundation for investigating the functional outcomes of CB1-Gs signaling.
  • This research paves the way for designing improved therapeutics targeting the CB1 receptor and the endocannabinoid system.