Characterization of the Binding Sites for Bacterial Acyl Homoserine Lactones (AHLs) on Human Bitter Taste Receptors (T2Rs)
Bibliographic record
Abstract
The 25 bitter taste receptors (T2Rs) in humans are novel players in mediating host-pathogen responses in the airways and innate immunity. The chemosensory T2Rs are expressed in different extraoral tissues and perform diverse pathophysiological roles from mediating bronchodilation to detecting bacterial infection in the airways. T2Rs were suggested to be activated by multiple bacterial quorum sensing molecules (QSMs). However, whether bacterial QSMs bind to T2Rs and the structural features on T2Rs has not yet been characterized. Here, we analyzed the taste sensory profiles of QSMs including acyl homoserine lactones (C4-AHL, C8-AHL, and 3-oxo-C12-AHL) and hydroxyquinolones (HHQ and NHQ) predominantly secreted by Gram-negative bacteria and characterized the candidate T2Rs interacting with different QSMs using structure-function approaches. The potency of the above QSMs for T2Rs significantly expressed in the airways, namely T2R4, T2R14, and T2R20, was characterized. 3-Oxo-C12-AHL activated T2R4, T2R14, and T2R20, while C8-AHL activated T2R4 and T2R14 with strong potency. The T2R amino acid residues involved in the interactions were characterized by molecular-model-guided site-directed mutagenesis. AHLs bind to a similar orthosteric site present on the extracellular surface in all three T2Rs with significant contributions from residues in extracellular loop 2. Our results reveal the mode of binding of AHLs for different T2Rs and provide biochemical insights into their interactions. This study will facilitate mechanistic studies aimed at understanding the role of these T2Rs as "sensors" of bacteria and in host-pathogen interactions.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".