Calcium-sensing receptor involved in the oral perception of kokumi substances

Taste is a key determinant of food preference and involves basic tastes and complex sensations such as mouthfeel. To understand taste at a molecular level, researchers have used cryo-electron microscopy (cryo-EM) to determine the structures of taste receptors. Cryo-EM has also been applied to analyze the interactions between food components and biological systems, playing a vital role in food science. A key example is the calcium-sensing receptor (CaSR), a class C G-protein-coupled receptor (GPCR) essential for the oral perception of kokumi substances, which are taste modulators. We used cryo-EM to determine the structure of CaSR complexed with γ-glutamyl-valyl-glycine (γ-EVG), a potent kokumi peptide. This analysis identified the precise site and key residues of CaSR involved in binding γ-EVG. Identification of the molecular basis of kokumi peptide recognition facilitates the rational design of novel taste modulators for the food industry.