Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins
- 6 August 2006
- journal article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 13 (9), 772-777
- https://doi.org/10.1038/nsmb1129
Abstract
Heptahelical receptors activate intracellular signaling pathways by catalyzing GTP for GDP exchange on the heterotrimeric G protein α subunit (Gα). Despite the crucial role of this process in cell signaling, little is known about the mechanism of G protein activation. Here we explore the structural basis for receptor-mediated GDP release using electron paramagnetic resonance spectroscopy. Binding to the activated receptor (R*) causes an apparent rigid-body movement of the α5 helix of Gα that would perturb GDP binding at the β6-α5 loop. This movement was not observed when a flexible loop was inserted between the α5 helix and the R*-binding C terminus, which uncouples R* binding from nucleotide exchange, suggesting that this movement is necessary for GDP release. These data provide the first direct observation of R*-mediated conformational changes in G proteins and define the structural basis for GDP release from Gα.Keywords
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