Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste - PubMed (original) (raw)

. 2005 Apr 15;280(15):15238-46.

doi: 10.1074/jbc.M414287200. Epub 2005 Jan 24.

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• PMID: 15668251
• DOI: 10.1074/jbc.M414287200

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Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste

Peihua Jiang et al. J Biol Chem. 2005.

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Abstract

The detection of sweet-tasting compounds is mediated in large part by a heterodimeric receptor comprised of T1R2+T1R3. Lactisole, a broad-acting sweet antagonist, suppresses the sweet taste of sugars, protein sweeteners, and artificial sweeteners. Lactisole's inhibitory effect is specific to humans and other primates; lactisole does not affect responses to sweet compounds in rodents. By heterologously expressing interspecies combinations of T1R2+T1R3, we have determined that the target for lactisole's action is human T1R3. From studies with mouse/human chimeras of T1R3, we determined that the molecular basis for sensitivity to lactisole depends on only a few residues within the transmembrane region of human T1R3. Alanine substitution of residues in the transmembrane region of human T1R3 revealed 4 key residues required for sensitivity to lactisole. In our model of T1R3's seven transmembrane helices, lactisole is predicted to dock to a binding pocket within the transmembrane region that includes these 4 key residues.

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