Structural basis of cholecystokinin receptor binding and regulation

Two structurally-related guanine nucleotide-binding protein-coupled receptors for two related peptides, cholecystokinin (CCK) and gastrin, have evolved to exhibit substantial diversity in specificity of ligand recognition, in their molecular basis of binding these ligands, and in their mechanisms of biochemical and cellular regulation. Consistent with this, the CCK₁ and CCK₂ receptors also play unique and distinct roles in physiology and pathophysiology. The paradigms for ligand recognition and receptor regulation and function are reviewed in this article, and should be broadly applicable to many members of this remarkable receptor superfamily. This degree of specialization is instructive and provides an encouraging basis for the diversity of potential drugs targeting these receptors and their actions that can be developed.