Structural basis of G <sub>s</sub> and G <sub>i</sub> recognition by the human glucagon receptor
Anna Qiao, Shuo Han, Xinmei Li, Zhixin Li, Peishen Zhao, Antao Dai, Rulve Chang, Linhua Tai, Qiuxiang Tan, Xiaojing Chu, Limin Ma, Thor S. Thorsen, Steffen Reedtz‐Runge, Dehua Yang, Ming‐Wei Wang, Patrick M. Sexton, Denise Wootten, Fei Sun, Qiang Zhao, Beili Wu
Abstract
Choosing a partner that fits G protein–coupled receptors (GPCRs) are responsible for transducing diverse signals from outside to inside cells. This process requires specificity both in ligand binding to GPCRs and in coupling between GPCRs and their intracellular partners, G proteins. Qiao et al. determined the structure of the human glucagon receptor (GCGR), a type B GPCR, bound to glucagon and one of two heterotrimeric G proteins, G s or G i1 . GCGR signals mainly through G s , and the structures provide a basis for this specificity. Conformational changes in GCGR, relative to the inactive state, create a binding cavity for the G proteins. The pocket is opened sufficiently to accommodate a bulky binding motif in G s . G i1 can still bind but the pocket does not close around it, so there is a smaller interaction interface. Science , this issue p. 1346