A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6
Bibliographic record
Abstract
Significance Ykt6 is a conserved SNARE that plays critical roles along multiple vesicular pathways. To achieve its function, Ykt6 cycles between the cytosol and membrane-bound compartments through reversible lipidation. The mechanism that regulates these transitions is unknown. Ykt6 function is disrupted by α-synuclein, a protein critically implicated in synucleinopathies such as Parkinson’s Disease. Through a multidisciplinary approach, we report that phosphorylation regulated by Ca 2+ signaling drives a conformational change that allows Ykt6 to switch from a closed cytosolic to an open membrane-bound form. Phosphorylation is also a critical determinant for Ykt6 protein interactions with functional consequences in the secretory and autophagy pathways under normal and α-synuclein conditions. This work provides a mechanistic insight into Ykt6 regulation with therapeutic implications for synucleinopathies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".