Novel gurmarin-like peptides from <i>Gymnema sylvestre</i> and their interactions with the sweet taste receptor T1R2/T1R3
Bibliographic record
Abstract
Gymnema sylvestre (GS) is a traditional medicinal plant known for its hypoglycemic and hypolipidemic effects. Gurmarin (hereafter Gur-1) is the only known active peptide in GS. Gur-1 has a suppressive sweet taste effect in rodents but no or only a very weak effect in humans. Here, 8 gurmarin-like peptides (Gur-2 to Gur-9) and their isoforms are reported in the GS transcriptome. The molecular mechanism of sweet taste suppression by Gur-1 is still largely unknown. Therefore, the complete architecture of human and mouse sweet taste receptors T1R2/T1R3 and their interaction with Gur-1 to Gur-9 were predicted by AlphaFold-Multimer (AF-M) and validated. Only Gur-1 and Gur-2 interact with the T1R2/T1R3 receptor. Indeed, Gur-1 and Gur-2 bind to the region of the cysteine-rich domain (CRD) and the transmembrane domain (TMD) of the mouse T1R2 subunit. In contrast, only Gur-2 binds to the TMD of the human T1R2 subunit. This result suggests that Gur-2 may have a suppressive sweet taste effect in humans. Furthermore, AF-M predicted that Gα-gustducin, a protein involved in sweet taste transduction, interacts with the intracellular domain of the T1R2 subunit. These results highlight an unexpected diversity of gurmarin-like peptides in GS and provide the complete predicted architecture of the human and mouse sweet taste receptor with the putative binding sites of Gur-1, Gur-2, and Gα-gustducin. In addition, gurmarin-like peptides may serve as promising drug scaffolds for the development of antidiabetic molecules.
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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".