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.
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The authors thank N. R. Latorraca for critical reading of the manuscript and insightful suggestions. This work was supported by National Institutes of Health grants R01NS028471 and R01GM083118 (B.K.K.), the German Academic Exchange Service (DAAD) (D.H.) and the American Heart Association Postdoctoral fellowship (17POST33410958) (M.M.). B.K.K. is supported by the Chan Zuckerberg Biohub.
B.K.K. is a cofounder and consultant for ConfometRx, Inc.
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