The Conformational Dynamics of Heterotrimeric G Proteins During GPCR-Mediated Activation

Abstract

Heterotrimeric G proteins (G proteins) are essential cellular signaling proteins that mediate extracellular signals to achieve various cellular functions. G-protein-coupled receptors (GPCRs) are the major guanine nucleotide exchange factors (GEFs) that induce G proteins to release guanosine diphosphate and rapidly bind to guanosine triphosphate, resulting in G protein activation. G proteins undergo dynamic conformational changes during the activation/inactivation process, and the precise structural mechanism of GPCR-mediated G protein activation is of great interest. Over the last decade, a number of GPCR-G protein complex structures have been identified, yet an understanding of the mechanisms underlying allosteric conformational changes during receptor-mediated G protein activation and GPCR-G protein coupling selectivity is only now emerging. This review discusses recent studies on the dynamic conformational changes of G proteins and provides insight into the structural mechanism of GPCR-mediated G protein activation.