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Related Concept Videos

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...
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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.
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

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.
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...
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...
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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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay

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G-protein-coupled receptor dynamics: dimerization and activation models compared with experiment.

Bruck Taddese1, Lisa M Simpson, Ian D Wall

  • 1School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, U.K.

Biochemical Society Transactions
|March 23, 2012
PubMed
Summary

Molecular dynamics models of the beta-2 adrenergic receptor (β2AR) active state align well with G-protein-coupled receptor (GPCR) X-ray structures, offering insights into receptor activation and dimerization.

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Last Updated: May 23, 2026

G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
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Published on: September 10, 2016

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Area of Science:

  • Structural Biology
  • Computational Chemistry
  • Pharmacology

Background:

  • Previously developed molecular dynamics models of the active beta-2 adrenergic receptor (β2AR) state.
  • Recent advancements in X-ray crystallography of activated G-protein-coupled receptors (GPCRs).

Purpose of the Study:

  • Compare β2AR active state models with new GPCR X-ray structures.
  • Validate and refine computational models using experimental data.
  • Investigate GPCR dimerization and ligand interactions.

Main Methods:

  • Molecular dynamics simulations incorporating experimental biophysical data.
  • Virtual screening for agonist enrichment.
  • Comparative analysis of structural models and X-ray crystallographic data.
  • Re-analysis of photoaffinity labeling data for GPCR dimerization.

Main Results:

  • High agreement between β2AR active model and X-ray structures in transmembrane and binding regions.
  • Microswitch features reproduced with minor variations, particularly the rotamer toggle switch.
  • Identification of key residues involved in G-protein interaction.
  • Evidence supporting transmembrane helix 4 (TM4) at the GPCR dimer interface.
  • Insights into bivalent ligand passage between receptor helices.

Conclusions:

  • Computational models effectively capture key features of GPCR active states.
  • Structural insights into GPCR activation mechanisms and G-protein coupling.
  • Enhanced understanding of GPCR dimerization and its implications for drug design.
  • Comparison highlights the utility of both implicit and explicit solvent models in active-state simulations.