Bioluminescence resonance energy transfer-based biosensors allow monitoring of ligand- and transducer-mediated GPCR conformational changes
Bibliographic record
Abstract
G protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate a variety of cellular response which make them a target of choice for drug development in many indications. It is now well established that GPCRs can adopt several distinct conformations that can be differentially stabilized by various ligands resulting in different biological outcomes, a concept known as functional selectivity. However, due to the highly hydrophobic nature of GPCRs, tools to monitor these conformational ensembles are limited and addressing their conformation dynamics remains a challenge with current structural biology approaches. Here we describe new bioluminescent resonance energy transfer-based biosensors that can probe the conformational rearrangement promoted by ligands with different signaling efficacies as well as the impact of transducers such as G proteins and β-arrestin on these conformational transitions. The design of such sensors for other receptors should be useful to further explore the structural determinants of GPCR functional selectivity.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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".