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

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

12.1K
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...
12.1K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

7.2K
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...
7.2K
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

2.0K
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,...
2.0K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

5.6K
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...
5.6K
GPCR Desensitization01:12

GPCR Desensitization

6.1K
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...
6.1K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K

You might also read

Related Articles

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

Sort by
Same author

Prkar1a haploinsufficiency ameliorates the growth hormone excess phenotype in Aip-deficient mice.

Human molecular genetics·2020
Same author

Letter to the Editor from Berthon: "Cardiac Myxoma Caused by Fumarate Hydratase Gene Deletion in Patient With Cortisol-Secreting Adrenocortical Adenoma".

The Journal of clinical endocrinology and metabolism·2020
Same author

A Century After the Description of "Hormones", Our Golden Jubilee Celebration Goes on with What is New in Endocrine Oncology: And a Lot is New!

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme·2020
Same author

Curative resection of an aldosteronoma causing primary aldosteronism in the second trimester of pregnancy.

Endocrinology, diabetes & metabolism case reports·2020
Same author

c-KIT oncogene expression in PRKAR1A-mutant adrenal cortex.

Endocrine-related cancer·2020
Same author

Recovery of hypothalamic-pituitary-adrenal axis in paediatric Cushing disease.

Clinical endocrinology·2020

Related Experiment Video

Updated: Jul 10, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

8.9K

GPR101: Modeling a constitutively active receptor linked to X-linked acrogigantism.

Stefano Costanzi1, Lea G Stahr1, Giampaolo Trivellin2

  • 1American University, Department of Chemistry, Washington, DC, USA.

Journal of Molecular Graphics & Modelling
|November 25, 2023
PubMed
Summary

Genetic gigantism (X-LAG) is linked to overactive GPR101. This study provides structural insights into GPR101, revealing its constitutive activity and paving the way for potential X-LAG treatments.

Keywords:
AlphaFoldAlphaFold-multistateG protein-coupled receptors (GPCRs)GPR101Homology modelingMolecular dynamics

More Related Videos

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
14:02

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

8.5K
Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
16:16

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

Published on: September 13, 2013

15.3K

Related Experiment Videos

Last Updated: Jul 10, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

8.9K
Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
14:02

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

8.5K
Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
16:16

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

Published on: September 13, 2013

15.3K

Area of Science:

  • Biochemistry
  • Genetics
  • Pharmacology

Background:

  • GPR101, a G protein-coupled receptor (GPCR), is associated with X-linked acrogigantism (X-LAG), a rare genetic disorder.
  • X-LAG results from GPR101 gene microduplications on the X-chromosome, leading to receptor overexpression in pituitary tumors.
  • GPR101 is constitutively active, signaling without ligands and activating multiple G protein pathways (Gs, Gq/11, G12/13).

Purpose of the Study:

  • To investigate the structural basis of GPR101's constitutive activity.
  • To explore GPR101's potential as a therapeutic target for X-LAG.
  • To compare GPR101 structure with related GPCRs to understand ligand specificity.

Main Methods:

  • Homology modeling using in-house and AlphaFold-derived models.
  • Molecular dynamics simulations to analyze constitutive activity.
  • Structural comparison with closely related GPCRs.

Main Results:

  • Structural models of GPR101 were generated, providing insights into its conformation.
  • Molecular dynamics simulations confirmed the constitutive activation of GPR101.
  • Structural comparisons suggest GPR101 does not share natural ligands with its closest GPCR relatives.
  • Recent cryo-EM structures are available for further drug discovery.

Conclusions:

  • GPR101's constitutive activity is structurally supported, making it a viable target for X-LAG treatment.
  • Understanding GPR101 structure is crucial for developing inverse agonists.
  • Future research, aided by cryo-EM structures, can focus on computer-aided drug discovery for X-LAG.