title: Human sweet taste receptor mediates acid-induced sweetness of miraculin.
abstract: 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.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Koizumi
authors.forename: Asami
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Nakajima
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ito
authors.forename: Tohru
authors.initials: T
authors.lastname: Terada
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimizu-Ibuka
authors.forename: Loïc
authors.initials: L
authors.lastname: Briand
authors.forename: Tomiko
authors.initials: T
authors.lastname: Asakura
authors.forename: Takumi
authors.initials: T
authors.lastname: Misaka
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D002460:Cell Line; D005453:Fluorescence; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D013650:Taste Buds / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D043562:Receptors, G-Protein-Coupled; C008533:miraculin protein, Synsepalum dulcificum; C431926:taste receptors, type 1