Related Experiment Video
Updated: May 20, 2026

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
GDP release preferentially occurs on the phosphate side in heterotrimeric G-proteins
Maxime Louet1, Jean Martinez, Nicolas Floquet
1Institut des Biomolécules Max Mousseron-IBMM, CNRS UMR5247, Université Montpellier 1, Université Montpellier 2, Faculté de Pharmacie, Montpellier, France.
Abstract:
After extra-cellular stimulation of G-Protein Coupled Receptors (GPCRs), GDP/GTP exchange appears as the key, rate limiting step of the intracellular activation cycle of heterotrimeric G-proteins. Despite the availability of a large number of X-ray structures, the mechanism of GDP release out of heterotrimeric G-proteins still remains unknown at the molecular level. Starting from the available X-ray structure, extensive unconstrained/constrained molecular dynamics simulations were performed on the complete membrane-anchored Gi heterotrimer complexed to GDP, for a total simulation time overcoming 500 ns. By combining Targeted Molecular Dynamics (TMD) and free energy profiles reconstruction by umbrella sampling, our data suggest that the release of GDP was much more favored on its phosphate side. Interestingly, upon the forced extraction of GDP on this side, the whole protein encountered large, collective motions in perfect agreement with those we described previously including a domain to domain motion between the two ras-like and helical sub-domains of G(α).
More Related Videos
07:41A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
09:40Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
Related Concept Videos
Activation and Inactivation of G Proteins
GTPases and their Regulation
Large G-proteins, also known...
GTPases and their Regulation
Large G-proteins, also known...
G-protein Coupled Receptors
G-protein Coupled Receptors
IP3/DAG Signaling Pathway