Science ( IF 41.845 ) Pub Date : 2020-07-31 , DOI: 10.1126/science.abc9291 Guillaume Lebon
G protein–coupled receptors (GPCRs) are eukaryotic plasma membrane receptors that are organized into four classes in humans: A, B, C, and Frizzled. They internalize extracellular stimuli by activating a common pool of intracellular signaling partners such as the heterotrimeric G proteins (composed of Gα, β, and γ subunits) that subsequently induce an appropriate cellular response. Recent advances in cryo–electron microscopy (cryo-EM) enables challenging structures of GPCR signaling complexes to be solved, providing unprecedented insights about the molecular basis of their signal transduction (1). Qiao et al. (2) reported two cryo-EM structures of the class B human glucagon receptor (GCGR) Gs and Gi complexes, which helped clarify GCGR G protein selectivity. On page 523 of this issue, Hilger et al. (3) report a cryo-EM structure of a GCGR-Gs complex and reveal the effect of conformational changes on GCGR signaling properties. These studies support a common mechanism for class B receptor activation.