Journal of Molecular Neuroscience

, Volume 66, Issue 2, pp 207–213 | Cite as

The Heptahelical Domain of the Sweet Taste Receptor T1R2 Is a New Allosteric Binding Site for the Sweet Taste Modulator Amiloride That Modulates Sweet Taste in a Species-Dependent Manner

  • Meng Zhao
  • Xiang-Qun Xu
  • Xuan-Yu Meng
  • Bo LiuEmail author


The activity of sweet taste receptor (heterodimeric T1R2 and T1R3) can be modulated by sweet regulators. The compound amiloride can inhibit the sweet sensitivity of the human sweet taste receptor. This study describes the species-dependent regulation of the response of sweet taste receptors by this sweet inhibitor. Amiloride inhibited the sweet taste response of humans and mice but not that of squirrel monkeys. Using human/squirrel monkey/mouse chimeric T1R2 and T1R3 receptors as well as the agonist perillartine (which can activate the single heptahelical domain of T1R2), we found that the heptahelical domain of T1R2 is the molecular determinant that mediates the species-dependent sensitivity to this sweet regulator. Compared to the sweet inhibitor lactisole (which acts on T1R3), amiloride has a different allosteric binding site on the sweet receptor, which is important new information for the design of novel sweet taste modulators that act on T1R2.


Amiloride Allosteric site Perillartine Sweet inhibitors Sweet taste receptor T1R2/T1R3 



We thank Dr. Meng Cui from the Department of Pharmaceutical Sciences, Northeastern University for his experimental assistant in this study.

Funding information

This work was supported by the Natural Science Foundation of China (31271118).

Supplementary material

12031_2018_1156_Fig5_ESM.png (1.7 mb)
Online Resource 1.

Overall structure of the sweet taste receptor. Schematic representations of the human heterodimeric sweet taste receptor T1R2/T1R3. The conserved VFTM, CRD, and HD domains are colored in red, lightgreen, and blue, respectively. This figure was generated with the program PyMOL. (PNG 1743 kb)

12031_2018_1156_MOESM1_ESM.tif (2.7 mb)
High resolution image (TIF 2750 kb)
12031_2018_1156_Fig6_ESM.png (82 kb)
Online Resource 2.

Sequence alignment of human, squirrel monkey, and mouse T1R2s. Conserved residues are indicated with an asterisk above the alignment, single and double dots represent amino acids with semiconservative and conservative characteristics. Gaps introduced during the alignment process are indicated as dashes. The conserved VFTM, CRD, and HD domains are underlined, boxed, and lined in bold, respectively. The TMs 1-7 in the HD region are shaded with grey color. (PNG 82 kb)

12031_2018_1156_MOESM2_ESM.tif (239 kb)
High resolution image (TIF 238 kb)
12031_2018_1156_Fig7_ESM.png (82 kb)
Online Resource 3.

Sequence alignment of the human, squirrel monkey, and mouse T1R3s. Conserved residues are indicated with an asterisk above the alignment, single and double dots represent amino acids with semiconservative and conservative characteristics. Gaps introduced during the alignment process are indicated as dashes. The conserved VFTM, CRD, and HD domains are underlined, boxed, and lined in bold, respectively. The TMs 1-7 in the HD region are shaded with grey color. (PNG 81 kb)

12031_2018_1156_MOESM3_ESM.tif (241 kb)
High resolution image (TIF 241 kb)


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Copyright information

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Authors and Affiliations

  1. 1.School of Food Science and EngineeringQilu University of Technology (Shandong Academy of Sciences)JinanChina
  2. 2.Shandong Women’s UniversityJinanChina
  3. 3.School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Jiangsu Provincial Key Laboratory of Radiation Medicine and ProtectionSoochow UniversitySuzhouChina

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