Fig. 2: Binding modes of peptidic ligands and calcium at MC4R.
From: Structures of active melanocortin-4 receptor–Gs-protein complexes with NDP-α-MSH and setmelanotide
a–c Sphere representations of NDP-α-MSH (green carbon atoms), setmelanotide (purple carbon atoms), and SHU9119 (blue carbon atoms) bound into their respective binding sites in MC4R (clipped surface, orange, light-yellow, gray, respectively). d–f TM3 and TM6 receptor residues involved in peptide and/or Ca2+ interactions are highlighted. The bold red dashed line in d, e indicates no interactions of L1333.36 with agonist residue d-F1; the red dashed bidirectional arrow in e indicates a hydrophobic interaction between F2616.51 and setmelanotide d-F51 (Supplementary information, Table S6), and in f indicates an interaction between d-Nal41 of the antagonist SHU9119 and L1333.36. g–i Top view of d–f, highlighting all intermolecular hydrophilic interactions, assessed by a minimum distance of 3.5 Å (black dashed lines) (Supplementary information, Figs. S9–S11 and Tables S2–S5). NDP-α-MSH residues 4–11 are shown (g).
