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

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 Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
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...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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...

You might also read

Related Articles

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

Sort by
Same author

Alpha-synuclein-decorated nanoconjugates targeting alpha-synuclein assembly.

International journal of biological macromolecules·2026
Same author

B4GALT5 deficiency impairs glycosphingolipid biosynthesis: a new Congenital Disorder of Glycosylation?

Journal of lipid research·2026
Same author

LHCSR1 Functions as a Dimmer Switch for Light Harvesting.

The journal of physical chemistry letters·2026
Same author

Structure-Guided Prioritization and Synthesis of New Ligands for GPR17 Receptor.

ACS omega·2026
Same author

Mechanistic Insights into Lysine Cyclodeaminase Catalysis.

ACS omega·2026
Same author

Adenosine Receptor Functionality and Desensitization Machinery in a Neuronal Cell Model of Angelman Syndrome.

Journal of developmental biology·2026

Related Experiment Video

Updated: Jul 14, 2026

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
08:33

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time

Published on: March 11, 2021

Sodium Ions Affect GPR17 Conformational States and Functionality.

Luca Palazzolo1, Simona Daniele2, Davide Bianchi1

  • 1Dipartimento di Scienze Farmacologiche e Biomolecolari "Rodolfo Paoletti", Università degli Studi di Milano, Milan, Italy.

Proteins
|July 12, 2026
PubMed
Summary

Ionic sodium stabilizes the inactive conformation of G protein-coupled receptor 17 (GPR17). Mutating sodium-binding residues favors an active GPR17 state, aiding receptor purification and crystallization for drug discovery.

Keywords:
GPR17allosteric modulationradioligand bindingsite‐directed mutagenesissodium ions

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

Related Experiment Videos

Last Updated: Jul 14, 2026

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
08:33

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time

Published on: March 11, 2021

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

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Sodium ions (Na+) act as allosteric modulators for class-A G protein-coupled receptors (GPCRs), influencing their active and inactive conformational states.
  • Understanding sodium's role is crucial for optimizing GPCR crystallization, a key step in drug development.

Purpose of the Study:

  • To investigate the role of Na+ in regulating the conformational states of G protein-coupled receptor 17 (GPR17).
  • To assess the impact of mutations in sodium-binding residues (D77 and D293) on GPR17 binding, function, and conformation.
  • To evaluate the potential of these mutated variants for improved receptor purification and crystallization.

Main Methods:

  • Molecular dynamics (MD) simulations of wild-type and mutated GPR17 (D77A, D293N) in inactive and active states.
  • In vitro studies using receptor variants with mutations at D77 and D293.
  • Radioligand binding assays with GPR17-selective ligands.
  • Functional assays measuring G protein coupling and cAMP accumulation inhibition.

Main Results:

  • MD simulations indicated Na+ stabilizes the inactive GPR17 conformation by interacting with D77/D293, with this interaction breaking in the active state.
  • In vitro binding studies showed no significant change in GPR17 ligand binding affinity for mutated variants.
  • Mutations at D77 and D293 significantly increased G protein coupling and ligand potency in inhibiting cAMP accumulation, suggesting a shift towards an active receptor conformation.

Conclusions:

  • Ionic sodium stabilizes an inactive conformation of GPR17.
  • Mutations in sodium-binding residues disrupt ion binding, favoring a more active GPR17 conformation.
  • These active-state GPR17 variants are promising for homogeneous receptor purification and crystallization, facilitating structural studies and drug design.