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Apart from the substitution of protein residues, an extra sequence connected to the N-terminal or C-terminal could change the biased interactions between the ligand and receptor

The gut peptides signaling to the hypothalamus act via the ARC to mediate the appetite stimulation (+) effect through the activation of neurons containing neuropeptide Y (NPY) and Agouti-Related Peptide (AgRP) or appetite-inhibitory effects (-) via neurons containing the preopiomelanocortin (POMC)-derived alpha-melanocyte stimulating hormone (alpha-MSH) and cocaine and amphetamine regulated transcript (CART) peptide to hunger centers in the LHA, the satiety center in PVN in the medial hypothalamus (16)

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The Childrens Depression, Inventory (CDI)

Garcia-Gareta, E., Perez, M