Related Experiment Video
Updated: Dec 27, 2025

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Gαi1
Levi J McClelland1, Kaiming Zhang2, Tung-Chung Mou1,3
1Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT, 59812, USA.
Abstract:
Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Gα) and serves as an essential Gα chaperone. Mechanisms by which Ric-8A catalyzes these activities, which are stimulated by Casein Kinase II phosphorylation, are unknown. We report the structure of the nanobody-stabilized complex of nucleotide-free Gα bound to phosphorylated Ric-8A at near atomic resolution by cryo-electron microscopy and X-ray crystallography. The mechanism of Ric-8A GEF activity differs considerably from that employed by G protein-coupled receptors at the plasma membrane. Ric-8A engages a specific conformation of Gα at multiple interfaces to form a complex that is stabilized by phosphorylation within a Ric-8A segment that connects two Gα binding sites. The C-terminus of Gα is ejected from its beta sheet core, thereby dismantling the GDP binding site. Ric-8A binds to the exposed Gα beta sheet and switch II to stabilize the nucleotide-free state of Gα.
More Related Videos
Related Concept Videos
Activation and Inactivation of G Proteins
G-protein Coupled Receptors
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
GTPases and their Regulation
Large G-proteins,...
GTPases and their Regulation
Coat Assembly and GTPases
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...

