The conformational transition during G protein–coupled receptor (GPCR) and G protein interaction

Abstract

The precise structural mechanism of G protein–coupled receptor (GPCR)–G protein coupling has been of significant research interest because it provides fundamental knowledge on cellular signaling and valuable information for GPCR-targeted drug development. Over the last decade, several GPCR–G protein complex structures have been identified. However, these structures are mere snapshots of guanosine diphosphate (GDP)-released stable GPCR–G protein complexes, which have limited the understanding of the allosteric conformational transition during receptor binding to GDP release and the GPCR–G protein coupling selectivity. Recently, deeper insights into the mechanism underlying stepwise conformational changes during GPCR–G protein coupling were obtained using hydrogen/deuterium exchange mass spectrometry, hydroxyl radical footprinting-mass spectrometry, X-ray crystallography, cryoelectron microscopy, and molecular dynamics simulation techniques. This review summarizes these recent developments.