The sweet taste receptor: a single receptor with multiple sites and modes of interaction.
Elucidation of the molecular bases of sweet taste is very important not only for its intrinsic biological significance but also for the design of new artificial sweeteners. Up to few years ago design was complicated by the common belief that different classes of sweet compounds, notably sweet proteins, might interact with different receptors altogether. The recent identification and functional expression of the receptor for sweet taste have shown that there is but one receptor, drastically changing our approach to the development of new sweeteners. The explanation of how the sweet receptor can bind several different classes of molecules is that rather than multiple receptors there are, apparently, multiple sites on the single sweet taste receptor. In this chapter, the mechanisms of interaction of small and macromolecular sweet molecules will be examined, with particular emphasis on sweet proteins. Systematic homology modeling yields reliable models of all possible heterodimers of the human T1R2 and T1R3 sequences with the closed (A) and open (B) conformations of one of the metabotropic glutamate receptors (mGluR1), used as template. The most important result of these studies is the "wedge model," the first explanation of the taste of sweet proteins. In addition, it was shown that simultaneous binding to the A and B sites is not possible with two large sweeteners but is possible with a small molecule in site A and a large one in site B. This observation accounted for the first time for the peculiar phenomenon of synergy between some sweeteners.
Temussi
Pierandrea
P
Dipartimento di Chimica, Università di Napoli Federico II, Via Cinthia, Napoli I-80126, Italy.
D006801:Humans; D008970:Molecular Weight; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013549:Sweetening Agents / Q000378:metabolism*; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000378:metabolism* / Q000502:physiology*; D000098706:Taste Receptors, Type 2
D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; C431926:taste receptors, type 1; D000098706:Taste Receptors, Type 2