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Schematic illustration of the binding and pharmacological modulation of MRAP1-MC2R and RMAP2-GCGR pairs. Up panel: Binding of MRAP1 to MC2R and ACTH is a prerequisite for MC2R activation and ACTH-induced cAMP accumulation. Down panel: RAMP2 functions as a negative allosteric regulator of GCGR by enhancing extracellular receptor dynamics and stabilizing the inactive state of the intracellular surface.
