Human sweet taste receptor mediates acid-induced sweetness of miraculin

• DOI: 10.1073/pnas.1016644108
• Publication Date: 2011-09-27T06:26:14Z
• Authors: Ayako Koizumi; Asami Tsuchiya; Ken-ichiro Nakajima; Keisuke Ito; Tohru Terada; Akiko Shimizu-Ibuka; Loïc Briand; Tomiko Asakura; Takumi Misaka; Keiko Abe
• Keywords: Models, Molecular; 0301 basic medicine; Protein Conformation; 610; neoculin; insights; 630; Fluorescence; Cell Line; Receptors, G-Protein-Coupled; taste-modifying protein; Mice; 03 medical and health sciences; modifying protein; Animals; Humans; G protein-coupled receptor; umami taste; Glycoproteins; 0303 health sciences; molecular-mechanism; Hydrogen-Ion Concentration; Taste Buds; calcium imaging; [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition; positive allosteric modulator; miracle fruit; gymnemic acid; monkey; [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition

Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica . MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity.