Fig. 6. Intracellular interactions in the binding crevice between MC4R and Gs-protein.

a, b Intramolecular interactions at the IL2–TM3–TM6 site stabilizing the antagonized MC4R (PDB ID: 6w25¹⁶) (a), and the inactive β2AR (PDB ID: 2rh1⁶⁶) (b). c–e Overall view on MC4R–Gs with enlarged areas shown in d and e. Active receptor–Gs complex structures of MC4R bound to NDP-α-MSH (d), setmelanotide (e). f The corresponding boxed region (b) in the β2AR–Gs complex (PDB ID: 3sn6¹⁸) Black dashed lines indicate hydrophilic interactions.