Abstract
Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. The sweet taste induced by MCL is more intense when acidification occurs with weak acids as opposed to strong acids. MCL interacts with the human sweet receptor subunit hTAS1R2, but the mechanisms by which the acidification of MCL activates the sweet taste receptor remain largely unexplored. The work reported here speaks directly to this activation by utilizing a sweet receptor TAS1R2 + TAS1R3 assay. In accordance with previous data, MCL-applied cells displayed a pH dependence with citric acid (weak acid) being right shifted to that with hydrochloric acid (strong acid). When histidine residues in both the intracellular and extracellular region of hTAS1R2 were exchanged for alanine, taste-modifying effect of MCL was reduced or abolished. Stronger intracellular acidification of HEK293 cells was induced by citric acid than by HCl and taste-modifying effect of MCL was proportional to intracellular pH regardless of types of acids. These results suggest that intracellular acidity is required for full activation of the sweet taste receptor by MCL.
Highlights
Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice
We examined the effect of solution properties on the interaction of MCL with the sweet taste receptor using transient transfection of HEK293 cells by the sweet taste receptor, TAS1R2 + TAS1R3, along with Gα 16-gust[44]
A previous study suggested that the interaction site for MCL is the amino-terminal domain (ATD) of hTAS1R2 and the 448 to 494 amino acid residues in hTAS1R2 are required for the effect[9]
Summary
Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. Stronger intracellular acidification of HEK293 cells was induced by citric acid than by HCl and taste-modifying effect of MCL was proportional to intracellular pH regardless of types of acids These results suggest that intracellular acidity is required for full activation of the sweet taste receptor by MCL. One of the most puzzling and striking phenomena in human taste perception is the induction of a strong sweet taste by a sour acid when the sour acid is preceded by tasting a plant-based glycoprotein (itself having no taste) called miraculin (MCL)[1,2]. This 191 amino acid glycoprotein forms a homodimeric complex. We provide a molecular explanation for this remarkable phenomenon and argue that it provides new insights into the fundamental mechanisms underlying sour taste perception
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