Hydrophobic gasket mutation produces gating pore currents in closed human voltage-gated proton channels
Bibliographic record
Abstract
Significance A large family of membrane proteins, voltage-gated ion channels, regulate a vast array of physiological functions in essentially all life forms. How these molecules sense membrane potential and respond by creating ionic conduction is incompletely understood. The voltage sensors of these channels contain a “hydrophobic gasket,” a ring of hydrophobic amino acids near the center of the membrane, separating internal and external aqueous solutions. Although voltage-gated proton channels, H V 1, resemble voltage-sensing domains of other channels, they differ fundamentally. On depolarization, H V 1 conducts protons, whereas other voltage sensors open a physically distinct pore. We identify Val 109 , Phe 150 , Val 177 , and Val 178 as the hH V 1 hydrophobic gasket. Replacement with less hydrophobic amino acids accelerated channel opening and caused proton-selective leak through closed 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 | 0.001 | 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".