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  • D The effect of Q204A mutation in CCK2R on CCK-8-induced Gαq–Gγ dissociation.
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  • EC50 and pEC50 ± SEM were calculated using nonlinear regression (curve fit).
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In addition, CCK-8 stimulates both CCKRs and gastrin-17 is highly selective for CCK2R (Supplementary Fig. S1a)31,32. Apart from ligand selectivity, huge differences in downstream G protein signaling are present between CCK1R and CCK2R. CCK1R couples to the stimulatory G protein Gs and Gq (Fig. 1b; Supplementary Fig. S1b, c), and induces diverse effects under different pathophysiological conditions33. For example, CCK1R-activated Gq signaling is required for insulin secretion under low-glucose conditions, whereas Gs signaling contributes more strongly to insulin secretion under high-glucose conditions34.

The particles were extracted and subjected to 3D classification on the complex, and the best-resolved class was selected. The resulting set of 299,092 particles was subjected to CTF refinement, Bayesian polishing and 3D auto refinement using the pixel size of 1.014 Å. The final map has an indicated global resolution of 3.2 Å at a Fourier shell correlation (FSC) of 0.143.