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The key MRAP1-MC2R binding sites. (A) Ribbon model of the ACTH–MC2R–MRAP1 complex. MRAP1 interacts with the extracellular interface of the receptor and the agonist ACTH to secure specific binding of the ligand (PDB:8GY7). (B and C) Expanded views of the two MC2R-binding sites (B: S19; C: Y250) in the MRAP1-bound MC2R complex. (D) Sequence alignment of melanocortin receptors and other GPCRs interacting with MRAP1. Residues involved in MRAP1 regulation on MC2R are highlighted.
