Asynchronous subunit transitions prime acetylcholine receptor activation
Bibliographic record
Abstract
Communication at synapses is facilitated by postsynaptic receptors, which convert a chemical signal into an electrical response. For ligand-gated ion channels, agonist binding triggers rapid transitions through intermediate states leading to a transient open-pore conformation, with these transitions shaping the postsynaptic response. In this work, we determine structures of the muscle-type nicotinic acetylcholine receptor in unliganded, mono-liganded, and di-liganded states. Agonist binding to a single site stabilizes a closed structure where an entire principal agonist-binding subunit transitions to an active-like conformation, whereas the other unoccupied principal subunit remains inactive, albeit poised for activation. Uniting this intermediate structure with single-channel recordings informs a sequential activation mechanism where asynchronous subunit transitions prime the receptor for activation-a finding with implications for an entire superfamily of pentameric ligand-gated ion channels.
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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 | 0.001 |
| 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".