Allosteric conformational changes of G proteins upon its interaction with membrane and GPCR

Current resolved structures of GPCRs and G protein complexes provided important insights into G protein activation. However, the binding or dissociation of GPCRs with G protein is instantaneous and highly dynamic in the intracellular environment. The conformational dynamic of G protein still needs to be addressed. In this study, we applied F-19 solution NMR spectroscopy to monitor the conformational changes of G protein upon interact with detergent mimicking membrane and receptor. Our results show that there are two states equilibria in the Gain apo states. The interaction of G(alpha) with detergents will accelerate this conformational transformation and induce a state that tends to bind to GPCRs. Finally, the G(alpha) proteins presented a fully activation state when they coupled to GPCRs. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.