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Research Article

Human sweet taste receptor mediates acid-induced sweetness of miraculin

Ayako Koizumi, Asami Tsuchiya, Ken-ichiro Nakajima, Keisuke Ito, Tohru Terada, Akiko Shimizu-Ibuka, Loïc Briand, Tomiko Asakura, Takumi Misaka, and Keiko Abe
PNAS first published September 26, 2011; https://doi.org/10.1073/pnas.1016644108
Ayako Koizumi
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Asami Tsuchiya
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Ken-ichiro Nakajima
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Keisuke Ito
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Tohru Terada
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Akiko Shimizu-Ibuka
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Loïc Briand
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Tomiko Asakura
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Takumi Misaka
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  • For correspondence: aka7308@mail.ecc.u-tokyo.ac.jp amisaka@mail.ecc.u-tokyo.ac.jp
Keiko Abe
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  • For correspondence: aka7308@mail.ecc.u-tokyo.ac.jp amisaka@mail.ecc.u-tokyo.ac.jp
  1. Edited by David Julius, University of California, San Francisco, CA, and approved August 30, 2011 (received for review November 26, 2010)

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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.

  • G protein-coupled receptor
  • positive allosteric modulator
  • taste-modifying protein
  • calcium imaging

Footnotes

  • 1To whom correspondence may be addressed. E-mail: aka7308{at}mail.ecc.u-tokyo.ac.jp or amisaka{at}mail.ecc.u-tokyo.ac.jp.
  • Author contributions: A.K., T.M., and K.A. designed research; A.K., K.-i.N., T.T., and L.B. performed research; A.K., A.T., and K.I. contributed new reagents/analytic tools; A.K. and K.-i.N. analyzed data; and A.K., K.-i.N., T.T., A.S.-I., L.B., T.A., T.M., and K.A. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1016644108/-/DCSupplemental.

Freely available online through the PNAS open access option.

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Human sweet taste receptor mediates acid-induced sweetness of miraculin
Ayako Koizumi, Asami Tsuchiya, Ken-ichiro Nakajima, Keisuke Ito, Tohru Terada, Akiko Shimizu-Ibuka, Loïc Briand, Tomiko Asakura, Takumi Misaka, Keiko Abe
Proceedings of the National Academy of Sciences Sep 2011, 201016644; DOI: 10.1073/pnas.1016644108

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Human sweet taste receptor mediates acid-induced sweetness of miraculin
Ayako Koizumi, Asami Tsuchiya, Ken-ichiro Nakajima, Keisuke Ito, Tohru Terada, Akiko Shimizu-Ibuka, Loïc Briand, Tomiko Asakura, Takumi Misaka, Keiko Abe
Proceedings of the National Academy of Sciences Sep 2011, 201016644; DOI: 10.1073/pnas.1016644108
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