Sensitivity of human sweet taste receptor subunitsT1R2 andT1R3 to activation by glucose enantiomers

Nitzan Dubovski, Yaron Ben Shoshan Galeczki, Einav Malach, Masha Y. Niv*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

We have previously shown that l-glucose, the non-caloric enantiomer of d-glucose, activates the human sweet taste receptor T1R2/T1R3 transiently expressed in HEK293T cells. Here, we show that d- and l-glucose can also activate T1R2 and T1R3 expressed without the counterpart monomer. Serine mutation to alanine in residue 147 in the binding site of T1R3 VFT domain, completely abolishes T1R3S147A activation by either l- or d-glucose, while T1R2/T1R3S147A responds in the same way as T1R2 expressed without its counterpart. We further show that the original T1R2 reference sequence (NM_152232.1) is less sensitive by almost an order of magnitude than the reference sequence at the time this study was performed (NM_152232.4). We find that out of the four differing positions, it is the R317G in the VFT domain of T1R2, that is responsible for this effect in vitro. It is significant for both practical assay sensitivity and because glycine is found in this position in ~20% of the world population. While the effects of the mutations and the partial transfections were similar for d and l enantiomers, their dose–response curves remained distinct, with l-glucose reaching an early plateau.

Original languageAmerican English
Article numberbjad005
JournalChemical Senses
Volume48
DOIs
StatePublished - 2023

Bibliographical note

Funding Information:
The authors thank Dr. R. F. Margolskee for the pcDNA3 of chimeric Gα16gust44 and Dr. Maik Behrens for the pcDNA3 of T1R3, and for the pcDNA5FRT PM of NM_152232.1. The authors also thank Dr. Yoav Peleg for the help with sequencing and site-directed mutagenesis; and for the construction of pcDNA5 of T1R2, pcDNA5 of T1R2S9C,I191V,I486V, pcDNA5 of T1R2S9C,R317G,I486V, pcDNA5 of T1R2R317G,I486V, pcDNA5 of T1R2R317G, and pcDNA3 of TIR3S147A. The data underlying this article are available in the article and in its online supplementary material.

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press. All rights reserved.

Keywords

  • SNP
  • Tas1R2
  • Tas1R3
  • cell-based
  • gustatory
  • sweetness

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