Fig. 4. Interaction between THIQ and MC4R.

a Detailed interaction of small-molecule THIQ (cyan) with MC4R (plum). Structure viewed from the extracellular side shows the interaction network of MC4R, THIQ and Ca²⁺. b Structure comparison of α-MSH with THIQ. The two ligands are aligned by the receptor. c THIQ-induced cAMP accumulation assays of the residues involved in THIQ binding. Bars represent differences in calculated α-MSH potency [pEC₅₀] for each mutant relative to the wild-type receptor (WT). Data are colored according to the extent of effect. ^nsP > 0.01, *P < 0.01, **P < 0.001 and ***P < 0.0001 (one-way ANOVA followed by Dunnett’s multiple comparisons test, compared with the response of WT). See Supplementary information, Tables S10 and S11 for detailed statistical evaluation and receptor expression levels.