Structure and dynamics of GPCR signaling complexes

G-protein-coupled receptors (GPCRs) relay numerous extracellular signals by triggering intracellular signaling through coupling with G proteins and arrestins. Recent breakthroughs in the structural determination of GPCRs and GPCR–transducer complexes represent important steps toward deciphering GPCR signal transduction at a molecular level. A full understanding of the molecular basis of GPCR-mediated signaling requires elucidation of the dynamics of receptors and their transducer complexes as well as their energy landscapes and conformational transition rates. Here, we summarize current insights into the structural plasticity of GPCR–G-protein and GPCR–arrestin complexes that underlies the regulation of the receptor’s intracellular signaling profile. In this Review, the authors discuss recent insights into the mechanism of GPCR signaling provided by structural and biophysical elucidation of receptor interactions with G proteins and arrestins.