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

Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

3.1K
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,...
3.1K
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

14.5K
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...
14.5K
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

126.6K
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.
126.6K
GPCR Desensitization01:12

GPCR Desensitization

7.0K
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...
7.0K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

6.2K
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...
6.2K
The Two-State Receptor Model01:29

The Two-State Receptor Model

2.7K
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...
2.7K

You might also read

Related Articles

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

Sort by
Same author

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

Nature communications·2026
Same author

GPR3 Ligands Discovered through Combined Virtual and Conformational Biosensor-Based Screening.

Journal of the American Chemical Society·2026
Same author

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

Journal of visualized experiments : JoVE·2026
Same author

The Concise Guide to PHARMACOLOGY 2025/26: G protein-coupled receptors.

British journal of pharmacology·2025
Same author

In silico docking yields small molecule negative allosteric modulators targeting the core of Frizzled 7.

Nature communications·2025
Same author

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

Journal of visualized experiments : JoVE·2025

Related Experiment Video

Updated: Nov 1, 2025

G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
09:12

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

Published on: September 10, 2016

9.8K

Residue 6.43 defines receptor function in class F GPCRs.

Ainoleena Turku1,2, Hannes Schihada1, Pawel Kozielewicz1

  • 1Karolinska Institutet, Department of Physiology & Pharmacology, Sec. Receptor Biology & Signaling, Biomedicum 6D, Stockholm, Sweden.

Nature Communications
|June 25, 2021
PubMed
Summary

Frizzled receptors (FZDs) activate differently than Smoothened (SMO), with FZDs showing a kinked TM6 structure. This study reveals significant functional diversity among FZD subtypes and between FZDs and SMO.

More Related Videos

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

3.4K
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

16.7K

Related Experiment Videos

Last Updated: Nov 1, 2025

G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
09:12

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

Published on: September 10, 2016

9.8K
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

3.4K
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

16.7K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Class F G protein-coupled receptors (GPCRs), including Frizzled (FZD) subtypes and Smoothened (SMO), are poorly understood.
  • While SMO activation involves cholesterol binding to its 7TM core, FZD activation mechanisms remain largely unknown.

Purpose of the Study:

  • To investigate FZD activation mechanisms using computational biology and experimental assays.
  • To compare FZD activation with SMO and explore functional diversity within FZDs.

Main Methods:

  • Computational biology approaches.
  • Mutational analysis of FZD receptor function.
  • Ligand binding assays.
  • Downstream signaling assays in living cells (G protein activation, DVL2 recruitment, TOPflash activity).

Main Results:

  • Frizzled receptors (FZDs) exhibit distinct activation-associated conformational changes compared to SMO.
  • FZDs typically present a kinked TM6 upon activation due to residue P6.43, unlike SMO's straight TM6.
  • Functional comparisons highlight significant diversity among FZD subtypes and between FZDs and SMO.

Conclusions:

  • FZD and SMO receptor activation pathways differ substantially, particularly in TM6 conformation.
  • The presence of P6.43 in FZDs contributes to a kinked TM6, a common GPCR feature.
  • Considerable functional heterogeneity exists within the FZD family and in comparison to SMO.