Structural insights into hormone recognition and G-protein coupling of the urotensin-II receptor
Bibliographic record
Abstract
Urotensin-II (U-II) is a potent vasoconstrictor peptide that interacts with the human urotensin-II receptor (UTR), a class A G protein-coupled receptor (GPCR) that primarily couples with G q proteins. In this study, we present the cryo-electron microscopy structure of the miniG q -coupled UTR bound to the potent UTR agonist P5U, providing insights into unique ligand recognition and activation mechanisms. Unlike typical linear peptides, the cyclic structure of P5U engages the receptor's transmembrane domains through key side chain interactions involving residues F6, W7, K8, and Y9, which are crucial for receptor activation. Comparative analysis with somatostatin receptors (SSTRs) reveals distinct ligand specificity, driven by variations in side chain composition. Notably, we identify F274 6.51 as the toggle switch residue in UTR, in contrast to the classical W 6.48 seen in other GPCRs. Our findings elucidate the structural basis for UTR's G q coupling specificity, highlighting unique Gα q interactions. This study advances the understanding of U-II signaling and offers a foundation for developing selective UTR modulators, with potential therapeutic implications for cardiovascular diseases linked to dysregulated U-II activity.
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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 | 0.001 |
| 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".