Structural Basis of Mannitol-Induced Activation of Human Taste Receptor PKD2L1

Sour taste is generally considered as a non-preferred taste, but many organisms, including humans, evolved to consume sour-tasting foods. PKD2L1 is a proton-activated sour taste receptor. In this study, we found that mannitol, known to produce a sweet taste, acts on hPKD2L1 in a concentration-dependent and pH-sensitive manner, and in silico protein-ligand complex modeling indicated that D523 of PKD2L1 was the critical binding residue. When comparing the Vmax value, it was confirmed that the wild type has 55.7 ± 2.94 but changed to 0 ± 0 in the D523A mutant type. Fermented kimchi maintains an average pH of 3.5–4.5, and this low-pH condition supports the production of sweet and sour tastes by mannitol. A considerable quantity of mannitol is produced by heterofermentative lactic acid bacteria during fermentation of kimchi, and the acidity of kimchi increases after fermentation, which may impart a unique sweet and refreshing taste compared with fresh kimchi. These findings indicate that the differences in mannitol-induced taste perception, especially sour taste, depend on pH levels, which could help explain the conjugative taste perception associated with fermented kimchi.