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Related Concept Videos

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...
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...
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.
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...

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Related Experiment Video

Updated: May 14, 2026

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
10:59

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Published on: August 17, 2022

Modeling active GPCR conformations.

Bruck Taddese1, Lisa M Simpson, Ian D Wall

  • 1School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex, United Kingdom.

Methods in Enzymology
|February 5, 2013
PubMed
Summary
This summary is machine-generated.

Modeling active states of G protein-coupled receptors (GPCRs) is advanced by studying the β(2)-adrenergic receptor-Gs complex. Molecular dynamics simulations provide insights into GPCR activation pathways and conformational changes.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Computational Chemistry

Background:

  • G protein-coupled receptors (GPCRs) are crucial cell surface receptors involved in numerous physiological processes.
  • Understanding GPCR active states is essential for drug discovery and development.
  • Modeling GPCRs presents challenges due to their dynamic nature and conformational flexibility.

Purpose of the Study:

  • To present various molecular dynamics (MD)-based approaches for modeling GPCR active states.
  • To discuss key applications of these modeling techniques.
  • To provide insights into the activation mechanisms of GPCRs.

Main Methods:

  • Molecular dynamics simulations of the β(2)-adrenergic receptor-Gs complex.
  • Utilizing homology modeling techniques for active-state modeling.
  • Simulating experimental molecular probes and addressing loop modeling.

Main Results:

  • MD simulations revealed insights into GPCR activation pathways, conformational changes, dimerization, hydration, the ionic lock, ligand binding, protonation, and sodium binding.
  • Crystallography and simulations indicate that agonist presence alone is insufficient for active state formation; G protein-binding region restraints are necessary.
  • The role of microswitches, including the rotamer toggle switch, in GPCR activation was discussed.

Conclusions:

  • The β(2)-adrenergic receptor-Gs complex serves as a significant advance in active-state GPCR modeling.
  • Explicit simulation of experimental probes is vital for understanding GPCR activation.
  • Virtual screening against active models should be approached cautiously, as major conformational changes occur intracellularly.