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Decoding of amidated aromatic Cterminus and sulfation by cholecystokinin receptors reveals conserved and divergent evolutionary mechanisms

Understanding how evolutionarily related receptors preserve recognition principles for conserved peptide post-translational modifications (PTMs) while acquiring new selectivity remains central to neuropeptide-G protein-coupled receptor (GPCR) biology. The Aplysia cholecystokinin (CCK) system provides an informative model, as its peptides combine two representative PTM-related features: an amidated aromatic C-terminus (RFamide/DFamide), and a dual-tyrosine sulfation pattern exceeding the single-site architecture typical of vertebrates.

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