{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTAS2R16 is a G protein‐coupled receptor expressed predominantly in taste receptor cells of the tongue where it plays a crucial role in the perception of bitterness. It is specifically activated by bitter β‐glucopyranosides—including salicin, gentiobiose, and related compounds—thereby linking the recognition of a common β‐glycosidic bond structure to the sensation of bitter taste. Functional studies in heterologous cells and human subjects have confirmed that the receptor’s activation exhibits characteristic concentration dependence and desensitization, underscoring its basic role in gustatory signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic variation at the TAS2R16 locus has been shown to markedly influence bitter taste sensitivity and is associated with broader physiological traits. A coding SNP (K172N) in the receptor’s ligand–binding domain sensitizes individuals to bitter β‐glucopyranosides and has been linked to differences in alcohol dependence risk. In addition, polymorphisms in and around TAS2R16 have been associated with variation in food preferences, inter‐individual taste perception, longevity, and even extraoral disease susceptibility. These observations underscore how allelic diversity at TAS2R16 contributes to interpopulation differences and influences both nutritional habits and health outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and computational studies of TAS2R16 have provided vital insights into its ligand–receptor interactions. Ligand docking simulations combined with site–directed mutagenesis and molecular dynamics investigations have identified key residues in transmembrane segments (TM3, TM5, and TM6) that govern the recognition of diverse β‐glycopyranoside agonists. These approaches not only delineate the dual binding modes that accommodate a variety of structurally distinct aglycons but have also been leveraged to predict the functional consequences of single amino acid substitutions, thereby advancing the design of potential bitter blockers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its conventional role in gustation, TAS2R16 has been implicated in extraoral processes that may influence inflammatory outcomes and disease. For instance, its expression in human gingival fibroblasts has revealed that activation by salicin can attenuate lipopolysaccharide–induced pro–inflammatory cytokine release by repressing intracellular cAMP elevation and inhibiting NF–κB nuclear translocation—a mechanism that may open therapeutic avenues for the management of periodontitis. Moreover, emerging evidence suggests that TAS2R16–mediated signaling could play a role in modulating chronic inflammation in colorectal tissues, further linking taste receptor variability to disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bernd Bufe, Thomas Hofmann, Dietmar Krautwurst, et al. 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