T1R2 - Taste receptor type 1 member 2 is aprotein that in humans is encoded by theTAS1R2gene.[5]
Thesweet taste receptor is predominantly formed as a dimer of T1R2 and T1R3 by which different organisms sense this taste. In songbirds, however, the T1R2 monomer does not exist, and they sense the sweet taste through the umami taste receptor (T1R1 and T1R3) as a result of an evolutionary change that it has undergone.[6]
Both T1R2 and T1R3 receptors belongs to the class CG protein-coupled receptor family that features a common structure comprised a large extracellular domain, called the venus flytrap domain (VFD), which is connected to a 7-helix TMD by a cysteine-rich domain (CRD). The canonical activation mechanism of class C GPCRs follows a multiple-step process that requires communication between the VFDs (housing the orthosteric-binding site) and the TMDs via the CRDs.[7] Although the main binding site for most sweet compounds was found to reside in the VFT domain of T1R2, the T1R2 protein is not functional without formation of the 2+3 heterodimer.[8][9]
Natural sweeteners interact with the orthosteric binding pocket, either of T1R2 or T1R3. The closure of the T1R2 extracellular domain involves the rotation of both T1R2 and T1R3 VFDs. The signal is then transmitted to the TMDs via the CRDs. It has also been shown that sweet proteins modulate the receptor by interacting with the CRD.Some artificial sweeteners as well as the inhibitor of the sweet taste receptor –lactisole, were shown to interact with the allosteric binding sites of one of the sub-units in the TMD.[7][10]
ATAS1R2 andTAS1R1 genes, is their spontaneous activity in the absence of the extracellular domains and binding ligands.[11] This may mean that the extracellular domain regulates function of the receptor by preventing spontaneous action as well as binding to activating ligands such assucrose.
The T1R2+3 receptor has been shown to respond to natural sugarssucrose,sorbitol andfructose, and to the artificial sweetenerssaccharin,acesulfame potassium,dulcin, guanidinoacetic acid,cyclamate,sucralose,alitame,neotame andneohesperidin dihydrochalcone (NHDC).[10] Research initially suggested that rat receptors did not respond to many other natural and artificial sugars, such asglucose andaspartame, leading to the conclusion that there must be more than one type of sweet taste receptor.[9] Contradictory evidence, however, suggested that cells expressing the human T1R2+3 receptor showed sensitivity to bothaspartame andglucose but cells expressing the rat T1R2+3 receptor were only slightly activated byglucose and showed noaspartame activation.[12] These results are inconclusive about the existence of another sweet taste receptor, but show that the T1R2+3 receptors are responsible for a wide variety of different sweet tastes. Finally, T1R2+3 responses to non-sugar natural sweeteners such as steviol glycosides from the leaves of the Stevia plant and sweet proteins like thaumatin, monellin, and brazzein.[10]Another surprising ligand of the T1R2+3 is D2O, also known as heavy water which was shown to activate the human T1R2+3 receptor.[13]
T1R2 andT1R1 receptors have been shown to bind toG proteins, most often thegustducin Gα subunit, although a gusducin knock-out has shown small residual activity. T1R2 andT1R1 have also been shown to activate Gαo and Gαi protein subunits.[11] This suggests that T1R1 and T1R2 areG protein-coupled receptors that inhibitadenylyl cyclases to decreasecyclic guanosine monophosphate (cGMP) levels intaste receptors.[14] Research done by creating knock-outs of common channels activated by sensory G-proteinsecond messenger systems has also shown a connection between sweet taste perception and thephosphatidylinositol (PIP2) pathway. The nonselective cationTransient Receptor Potential channel TRPM5 has been shown to correlate with both umami and sweet taste. Also, thephospholipase PLCβ2 was shown to similarly correlate with umami and sweet taste. This suggests that activation of the G-protein pathway and subsequent activation of PLC β2 and the TRPM5 channel in these taste cells functions to activate the cell.[15]
^Yousif, Ragheed Hussam, et al. "Exploring the Molecular Interactions between Neoculin and the Human Sweet Taste Receptors through Computational Approaches."Sains Malaysiana 49.3 (2020): 517-525.APA
^abSainz E, Cavenagh MM, LopezJimenez ND, Gutierrez JC, Battey JF, Northup JK, Sullivan SL (June 2007). "The G-protein coupling properties of the human sweet and amino acid taste receptors".Developmental Neurobiology.67 (7):948–959.doi:10.1002/dneu.20403.PMID17506496.S2CID29736077.
^Abaffy T, Trubey KR, Chaudhari N (June 2003). "Adenylyl cyclase expression and modulation of cAMP in rat taste cells".American Journal of Physiology. Cell Physiology.284 (6):C1420 –C1428.doi:10.1152/ajpcell.00556.2002.PMID12606315.S2CID2704640.
Spadaccini R, Trabucco F, Saviano G, Picone D, Crescenzi O, Tancredi T, Temussi PA (May 2003). "The mechanism of interaction of sweet proteins with the T1R2-T1R3 receptor: evidence from the solution structure of G16A-MNEI".Journal of Molecular Biology.328 (3):683–692.doi:10.1016/S0022-2836(03)00346-2.PMID12706725.
