May 24, 2024 - Our functional analysis identified cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator with direct agonist activity at TAS2R14. Moreover, the orthosteric pocket is connected to the allosteric site via an elongated cavity, which has a hydrophobic core rich in aromatic residues. Our findings provide insights into the ligand recognition of bitter taste receptors and suggest activities of TAS2R14 beyond bitter taste perception via intracellular allosteric tastants.

January 22, 2025 - If large enough, action potentials are evoked in receptor cells (Yoshida et al. 2018) and trigger the activation of voltage-gated ion channels, namely calcium homeostasis modulator 1 and 3 (CALMH1/3) (Taruno et al. 2013; Ma et al. 2018), through whose pores the taste bud neurotransmitter ATP (Finger et al. 2005) is released (Taruno et al. 2013; Ma et al. 2018). ... Mechanism of taste GPCR signal transmission exemplified for bitter taste.

2 weeks ago - This receptor is also found in ... which activates this receptor might cause excessive bladder contraction. Taste helps to identify toxins, maintain nutrition, and regulate appetite, immune responses, and gastrointestinal motility. Five basic tastes are recognized today: salty, sweet, bitter, sour, and ...

June 7, 2023 - Using a combined experimental-computational approach, the activation profiles of human and mouse bitter taste receptors, TAS2Rs and Tas2rs, by bile acids is described, suggesting a physiological role of bile acids for taste receptors in ...

February 18, 2026 - Scientists uncovered unique structural features of a bitter taste receptor, including a role for cholesterol in receptor activation.

April 11, 2024 - Researchers found that when bitter tastants come into contact with TAS2R14 receptors, the chemicals wedge themselves into to a specific spot on the receptor called an allosteric site, this causes the protein to change its shape, activating the ...

June 1, 2010 - Further mutagenesis identified additional residues important for receptor-specific agonist activation, indicating that interaction with such a variety of compounds is governed by more than two amino acids in TM7 and may as well include residues that are identical in hTAS2R43, -R31, and -R46. Another component affecting agonist selectivity of hTAS2Rs could be a tight access control for “wrong” bitter compounds.

Alkaloids are the most common bitter compounds, appearing in barks (quinine), fruits (berberine, piperine), seeds (xylopine, theobromine), and leaves (skimmianine), and activating a wide range of the TAS2Rs. Sesquiterpene lactones, notably in flowers (eg, chamomile), leaves (eg, wormwood), and roots (eg, dandelion, chicory), show strong activation of TAS2R46, suggesting this receptor plays a central role in detecting plant-derived lactones.

August 7, 2023 - In the case of bitter taste receptors, ... 15). These proteins activate the membrane-bound phospholipase C2 (PLCβ2), thus inducing the production of inositol-1,4,5-thriphosphate (IP3) and diacylglyceride (DAG) (1, 3)....

May 27, 2024 - Furthermore, not only did the bitter taste receptors (taste receptor type 2 family, T2Rs) show taste effects, but extra-oral T2Rs could also be activated by binding with bitter components, regulating physiological activities via modulating hormone ...

Moreover, for some of these broadly activating bitter compounds, it was shown that their “promiscuity” is an intrinsic feature that is not limited to the receptor repertoire of a single species but also allows the activation of multiple receptors of evolutionary distant species.4,5 An even higher level of complexity arose from the subsequent discovery of bitter taste receptor antagonists.6,7 These molecules are frequently bitter tastants that activate one or a subset of receptors but possess the capacity to suppress the activation of another subset of TAS2Rs, hence, their inhibitory function is surfacing only when mixtures of bitter substances are tasted.

2 weeks ago - Researchers found that when bitter tastants come into contact with TAS2R14 receptors, the chemicals wedge themselves into to a specific spot on the receptor called an allosteric site, this causes the protein to change its shape, activating the ...

Subject terms: Taste receptors, High-throughput screening · Using a combined experimental-computational approach, the activation profiles of human and mouse bitter taste receptors, TAS2Rs and Tas2rs, by bile acids is described, suggesting a physiological role of bile acids for taste receptors ...

April 20, 2026 - The data show that these T2R46 peptides can also activate T2R14, but with lower potencies than that of P5 (Fig. 5k and Supplementary Table 1), suggesting T2R14 prefers its own ECL2 sequence in comparison with corresponding ECL2 peptides of T2R46. Collectively, our data indicate strongly that ECL2 in the T2Rs may act as a tethered agonist that enables rapid response of the receptor to a diverse array of bitter tastants.

If large enough, action potentials are evoked in receptor cells (Yoshida et al. 2018) and trigger the activation of voltage-gated ion channels, namely calcium homeostasis modulator 1 and 3 (CALMH1/3) (Taruno et al. 2013; Ma et al. 2018), through whose pores the taste bud neurotransmitter ATP (Finger et al. 2005) is released (Taruno et al. 2013; Ma et al. 2018). ... Mechanism of taste GPCR signal transmission exemplified for bitter taste.

They play key roles in detecting potentially harmful compounds and orchestrating physiological responses in the respiratory, gastrointestinal and endocrine systems. Upon binding of bitter ligands, TAS2Rs couple to taste-specific G proteins and activate phospholipase Cβ2, leading to inositol ...

We investigated whether human bitter receptors (hTAS2Rs) recognize bitterness of peptides with a heterologous expression system. HEK293 cells expressing hTAS2R1, hTAS2R4, hTAS2R14, and hTAS2R16 responded to bitter casein digests. Among those cells, the hTAS2R1-expressing cell was most strongly activated by the synthesized bitter peptides Gly-Phe and Gly-Leu, and none of the cells was activated by the non-bitter dipeptide Gly-Gly.

April 10, 2024 - The structures suggest that different molecules modulate the receptor’s function at two distinct regions of the receptor, and that dual binding at these regions leads to complete activation.

Xu et al. determined the structures of the human bitter taste receptor TAS2R46 bound to a mini–G protein containing the TAS2R46-binding site from the G protein gustducin. The structures reveal distinct features of TAS2R46 compared with other GPCRs and provide insight into how ligands such as the bitter alkaloid strychnine activate this GPCR to evoke a bitter taste.

April 10, 2024 - Researchers found that when bitter tastants come into contact with TAS2R14 receptors, the chemicals wedge themselves into to a specific spot on the receptor called an allosteric site, this causes the protein to change its shape, activating the ...