Activation of the human sweet taste receptor T1R2/T1R3 by sugars and novel molecules

The sweet taste is an innately attractive taste modality, that leads to ingestion of nutritive high calorie food, and maintenance of glucose homeostasis in the body. (Dubovski et al., 2022) A wide variety of sweet molecules are recognized by the sweet taste receptor, including sugars, sweeteners, and sweet proteins. The canonical sweet taste receptor is a heterodimer consisting of two subtypes of type 1 taste receptor (TAS1Rs): TAS1R2 and TAS1R3, members of family C G protein-coupled receptors (GPCRs). Class C GPCRs are composed of an extracellular N-terminal Venus flytrap domain (VFD) which includes the orthostatic binding site; a cysteine rich domain (CRD) which contains nine conserved cysteines and function as the binding site of sweet proteins; and seven transmembrane C- terminal domain (TMD) which includes the allosteric binding site. To date, no experimental structure of a mammalian sweet taste receptor exists, and hence, predicted models(ben Shoshan-Galeczki & Niv, 2020) are used to better understand the receptor functioning. Functional assays using cells transiently transfected with the sweet taste system are also used for the measurement of ligand activation, by the detection of modulators in the taste signal cascade such as IP1, cAMP and Ca+2. Combining computational analysis alongside with cell-based assays, enable us to study the role of each receptor subunit, in the activation of the sweet taste receptor by di- and mono- saccharides and to identify novel and improved sweeteners.