Aspartame is a commercially available low-calorie sweetener widely used in foods and beverages. Aspartame preference and the ability to taste aspartame sweetness vary among mammalian species. Humans, apes and Old World monkeys perceive aspartame as sweet, but other primate species, and most of non-primate species, do not. We analysed the association of aspartame taster/non-taster status and sequence variants of the sweet taste receptor proteins, T1R2 and T1R3, in several species. Nine variant sites in T1R2 and 32 variant sites in T1R3 distinguished aspartame tasters and non-tasters. We next examined whether any of these variant sites disrupt interaction between aspartame and the T1R2+3 receptor. Molecular docking of aspartame to computer-generated models of the T1R2 + T1R3 receptor dimer identified primary active binding sites in the VFT domain of the T1R2 and T1R3 proteins. In addition, previously unknown allosteric sites were identified. Sequence variants at the T1R2 allosteric binding site (Figure 2) likely influence the interaction of aspartame with the primary binding site and ability of aspartame to activate the receptor, and therefore an animals’ ability to taste sweetness of aspartame.[78]
