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

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.