ArticleiScience2023
Predicted structure and cell signaling of TAS2R14 reveal receptor hyper-flexibility for detecting diverse bitter tastes.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Bitter taste TAS2R14 and TAS2R46 receptors bound to G proteins: comparison of cryo-EM, AlphaFold, and molecular dynamics structures.European biophysics journal : EBJ · 2026Article
- Dynamic Pathway Selectivity of TAS2R5 toward or Away from β-Arrestin or G Protein from Biased Agonists.Biochemistry · 2026Article
- Ethanol Regulates Bitterness Perception of the Trp-Ile-Lys-Lys (WIKK) Peptide by Activating the Human Bitter Receptor T2R47.Foods (Basel, Switzerland) · 2026Article
- Key bitterness compounds of cigar tobacco leaves and their molecular docking with human bitter receptors.Scientific reports · 2026Article
- Unraveling bitter peptides in wheat protein hydrolysates.Food chemistry. Molecular sciences · 2025Article
- Biological Actions of Bile Acids via Cell Surface Receptors.International journal of molecular sciences · 2025Review
- A deadly taste: linking bitter taste receptors and apoptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- TAS2R5 screening reveals biased agonism that fails to evoke internalization and downregulation resulting in attenuated desensitization.PloS one · 2025Article
- Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments.Communications chemistry · 2024Article
- Label-free, real-time monitoring of membrane binding events at zeptomolar concentrations using frequency-locked optical microresonators.Nature communications · 2024Article
- Exploring TAS2R46 biomechanics through molecular dynamics and network analysis.Frontiers in molecular biosciences · 2024Article
- Label-free, real-time monitoring of membrane binding events at zeptomolar concentrations using frequency-locked optical microresonators.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The 25 human bitter taste receptors (TAS2Rs) are expressed on taste and extra-oral cells representing an integrated chemosensory system. The archetypal TAS2R14 is activated by > 150 topographically diverse agonists, raising the question of how this uncharacteristic accommodation is achieved for these GPCRs. We report the computationally derived structure of TAS2R14 with binding sites and energies for five highly diverse agonists. Remarkably, the binding pocket is the same for all five agonists. The energies derived from molecular dynamics are consistent with experiments determining signal transduction coefficients in live cells. TAS2R14 accommodates agonists through the breaking of a TMD3 H-bond instead of the prototypic strong salt bridge, a TMD1,2,7 interaction different from Class A GPCRs, and agonist-promoted TMD3 salt bridges for high affinity (which we confirmed by receptor mutagenesis). Thus, the broadly tuned TAS2Rs accommodate diverse agonists via a single (vs multiple) binding pocket through unique TM interactions for sensing disparate micro-environments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.