Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

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...
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...
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...
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...
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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Discovery of an Orally Available Potent ER Aminopeptidase 1 (ERAP1) Inhibitor That Enhances Antitumor Responses and Limits Inflammatory Autoimmunity <i>In Vivo</i>.

Journal of medicinal chemistry·2026
Same author

Automated Molecular Design in BRADSHAW, Applied to the Optimization of ERAP1 Inhibitors.

Journal of medicinal chemistry·2026
Same author

In vivo functional profiling and structural characterization of the human <i>GLP1R</i> A316T variant.

Science advances·2026
Same author

Structural basis of modified ligand selectivity from N-terminal PAC1R alternative splicing.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

Shoulder Instability in Contact and Collision Athletes: A Focused Review on Assessment, Management, and Treatment.

Current sports medicine reports·2025
Same author

Hypoxia Exacerbates Inflammatory Signaling in Human Coronavirus OC43-Infected Lung Epithelial Cells.

Biomolecules·2025

Related Experiment Video

Updated: Jun 4, 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 GPCR active state conformations: the β(2)-adrenergic receptor.

Lisa M Simpson1, Ian D Wall, Frank E Blaney

  • 1Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, United Kingdom.

Proteins
|February 22, 2011
PubMed
Summary

Researchers developed a validated model of the active β(2)-adrenergic receptor conformation. This advanced model accurately predicts agonist binding and G protein interactions, offering a new tool for drug discovery.

More Related Videos

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
10:13

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

Published on: June 9, 2017

BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells
09:21

BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells

Published on: November 7, 2025

Related Experiment Videos

Last Updated: Jun 4, 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

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
10:13

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

Published on: June 9, 2017

BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells
09:21

BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells

Published on: November 7, 2025

Area of Science:

  • Structural Biology
  • Computational Chemistry
  • Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) are crucial drug targets, but modeling their active states remains challenging.
  • Recent advances in GPCR structural biology and opsin crystal structures provide new insights for homology modeling.

Purpose of the Study:

  • To generate a validated computational model of the active conformation of the β(2)-adrenergic receptor.
  • To assess the model's accuracy in predicting ligand binding and G protein interactions.

Main Methods:

  • Combined structural information from inactive and active GPCR states, including opsin.
  • Employed molecular dynamics simulations incorporating experimental data (zinc binding, spin labeling, spectroscopy).
  • Validated the model using manual docking, site-directed mutagenesis, and virtual screening.

Main Results:

  • Developed a robust model of the active β(2)-adrenergic receptor, highlighting conformational changes in TM6, TM5, and TM7.
  • Virtual screening accurately predicted selectivity for β-adrenergic agonists, stereoisomers, and receptor subtypes.
  • The model successfully docked a stimulatory G protein C-terminal peptide, consistent with experimental data.

Conclusions:

  • The generated active β(2)-adrenergic receptor model is extensively validated and agrees well with diverse experimental findings.
  • The model provides a powerful tool for understanding GPCR activation mechanisms and guiding drug design.
  • The employed methodology is transferable for modeling the active states of other GPCRs.