Structural insights into ligand recognition and subtype selectivity of the human melanocortin-3 and melanocortin-5 receptors | Cell Discovery

Researchers utilized cryo-electron microscopy to solve the structures of the human melanocortin-3 (MC3R) and melanocortin-5 (MC5R) receptors bound to various agonists. The findings reveal how the endogenous peptide γ-MSH achieves selectivity for MC3R through specific C-terminal interactions, while α-MSH binds non-selectively to MC5R. Additionally, the study characterizes the binding mode of a potent synthetic agonist, PG-901, and confirms the presence of calcium ions within the receptor structures.