The sweet taste in humans is mediated by the TAS1R2/TAS1R3 G protein-coupled receptor (GPCR), which belongs to the class C family that also includes the metabotropic glutamate and γ-aminobutyric acid receptors. We report here the predicted 3D structure of the fulllength TAS1R2/TAS1R3 heterodimer, including the Venus Flytrap Domains (VFDs) [in the closed-open (co) active conformation], the cysteine-rich domains (CRDs), and the transmembrane domains (TMDs) at the TM56/TM56 interface. We observe that binding of agonists to VFD2 of TAS1R2 leads to major conformational changes to form a TM6/TM6 interface between TMDs of TAS1R2 and TAS1R3, which is consistent with the activation process observed biophysically on the metabotropic glutamate receptor 2 homodimer. We find that the initial effect of the agonist is to pull the bottom part of VFD3/TAS1R3 toward the bottom part of VFD2/ TAS1R2 by ∼6 Å and that these changes get transmitted from VFD2 of TAS1R2 (where agonists bind) through the VFD3 and the CRD3 to the TMD3 of TAS1R3 (which couples to the G protein). These structural transformations provide a detailed atomistic mechanism for the activation process in GPCR, providing insights and structural details that can now be validated through mutation experiments.GPCR activation | class C GPCR | molecular dynamics | noncaloric sweetener G protein-coupled receptors (GPCRs) play an essential signaling function throughout all eukaryote systems, serving as the basis for detecting light, smell, nociceptive signaling, and taste along with dopamine, serotonin, adrenaline, etc. (1). Generally, binding of a signaling ligand to the exterior of a cell causes a G protein at the intracellular interface to dissociate, which then triggers a sequence of events that respond to the signal. There are now structures for ∼32 human GPCRs, including 4 that have been activated (2); however, a detailed understanding of the activation mechanisms of monomeric GPCRs is still lacking (3). This is most unfortunate because about half the drugs under development involve GPCRs and it is most important to know whether the drug will serve as an agonist to activate the G protein or as an antagonist or inverse agonist.Particularly interesting here are the class C GPCRs, which in addition to a seven-helix transmembrane domain (TMD) include a large N-terminal segment consisting of a Venus Flytrap Domain (VFD) and a cysteine-rich domain (CRD). Biophysical measurements on the class C glutamate dimer receptor 2 (mGluR2) have shown that the inactive or resting state (R) dimer interface involves contacts between TMs 4 and 5 of each TMD, whereas formation of the fully active state is associated with motions in which the extracellular (EC) projections of the two TM6s move together to form a TM6-TM6 interface (4).In addition, biophysical experiments on the class C sweet receptor, consisting of the TAS1R2/TAS1R3 heterodimer, indicate that sucrose and glucose bind to the VFD of both the TAS1R2 and TAS1R3 subunits (5, 6), whereas other sweeteners, such as aspartame and st...
A lexicon for lemon‐lime carbonated beverages (regular and diet) was developed to understand the flavor and mouthfeel attributes of lemon‐lime beverages. Descriptive analysis of 18 carbonated lemon‐lime or citrus beverages was performed by a highly trained panel. Analysis of variance and principle component analysis were used to interpret results. Key differentiating attributes of beverages were mouthfeel attributes (carbonation, bite, burn, numbing, after‐numbing, slipperiness, tongue heaviness), basic tastes (sour aftertaste, sour, bitter, bitter aftertaste, other aftertaste, metallic aftertaste) and aromatics (overall aroma, cooked lime/lemon, lemon candy). Beverages were distinguished based on category (sparkling or soda), sweetening systems (diet versus regular) and brand. Beverages in the soda category were characterized by high bite, burn, numbing, carbonation and after‐numb, whereas beverages in the sparkling beverage category were characterized by slipperiness, overall aroma, cooked lemon/lime, sour taste and sour aftertaste. Diet beverages were characterized by bitter, bitter aftertaste, metallic aftertaste and other aftertaste, while regular beverages were characterized by tongue heaviness and lemon candy. The developed lexicon allowed for documentation of multimodal sensory perceptions generated by carbonated beverages. PRACTICAL APPLICATION The development of a comprehensive lexicon for carbonated lemon‐lime beverages descriptive analysis allows a precise documentation of sensory properties of the complex system of lemon‐lime‐flavored carbonated beverages. These results will further enable the study of the effects of other ingredients such as stabilizers, flavoring systems and natural nonnutritive sweeteners on the sensory perception of beverages. Development of low caloric lemon‐lime carbonated beverages that maintain similar flavor profile and mouthfeel attributes of regular beverages is challenging and can be assisted when the impact of ingredients on the sensory perception on the whole scope of the beverage system is understood.
The objective of this study was to determine the ideal whole grain bread product for children (8-17 years) using a survey and conjoint analysis. Focus groups (three focus groups, n = 23), emotional response and appearance liking surveys (n = 172), and an adaptive choice-based conjoint survey (n = 173) were conducted with children. Across elementary, middle and high school-aged children, children preferred bread with a light crumb (inside of the bread), a light crust and no topping or added textures or visual cues in the crumb. Children had generally negative feelings for breads with dark-colored crumb and crust, but had generally positive feelings for breads with light-colored crumb and crust. Breads with white crumb were liked more than bread with dark crumb, regardless of crumb particles, crust or crust topping. Crust color had no impact on overall appearance liking score. These results demonstrate that regardless of age, children like soft breads with light-colored crumb and crust with no fillings or toppings. PRACTICAL APPLICATIONSIncreased consumption of whole grain breads is an effective technique in decreasing obesity in American children. Children's likings of bread products have an inverse relationship with whole grain versus refined grain content. This study demonstrated that development of a whole grain bread product that is desirable to children in both visual appearance and taste is an important step toward increased whole grain consumption by children and that images of attributes and a conjoint analysis in a survey format can be effectively utilized by children to measure their desires.
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