Fig. 3: Proton recognition mode of GPR4–G_q complex at physiological pH.

a The preserved interaction between H17^1.32 and H80^2.67. b The interaction between H79^2.66 and the common water molecule. c The extended polar network of H165^ECL2 and H269^7.36. The rotational direction of residues is labeled by a black arrow indicating the rotation of H165^ECL2, compared with H165^ECL2 in the GPR4–G_s complexes, and polar interactions are shown as orange dashed lines. d, e The special networks involving the water molecules in G_q-coupled GPR4. The water molecules are displayed as green spheres. The polar interactions are shown as orange dashed lines. f, g Effects of mutations on cAMP and IP1 accumulation responses. ΔpEC₅₀ represents the difference between pEC₅₀ values of GPR4 WT and mutants. U.D. means undetectable because the maximum activation level is below 50% to determine pEC₅₀ values (f). E_max values represent the maximum cAMP or IP1 accumulation induced by various pH conditions in GPR4 WT and mutants, which are normalized to WT (g). Heat map is generated on the basis of the pEC₅₀ or E_max. Values are shown as means of three independent experiments. The original data are provided in Supplementary Fig. S11.