N-terminal signals in the SNX-BAR paralogs Vps5 and Vin1 guide coat complex formation
Bibliographic record
Abstract
Abstract Endosomal coat complexes assemble by incorporating membrane-binding subunits such as those of the sorting nexin (SNX) family. The S. cerevisiae SNX-BAR paralogs Vin1 and Vps5 are respective subunits of the endosomal VINE and retromer complexes that arose from a fungal whole genome duplication. Interactions mediated by the Vin1 and Vps5 BAR domains are required for protein complex assembly and membrane association. However, a degree of promiscuity is predicted for yeast BAR-BAR pairings, suggesting that another mechanism guides the formation of specific endosomal coat complexes. Previous work by our group and others has implicated the unstructured N-terminal domains of Vin1 and Vps5 in complex assembly. Here, we map N-terminal signals in both SNX-BAR paralogs that contribute to the formation and function of two distinct endosomal coats in vivo . Whereas Vin1 leverages a polybasic region and adjacent hydrophobic motif to bind Vrl1 and form VINE, the N-terminus of Vps5 interacts with the retromer subunit Vps29 at two separate sites. We show that one of these Vps5 motifs binds to a conserved hydrophobic pocket in Vps29 that is shared with other accessory proteins and targeted by a bacterial virulence factor in humans. Lastly, we examined the sole isoform of Vps5 from the milk yeast K. lactis and found that ancestral yeasts may have used a nested N-terminal signal to form both VINE and retromer. Our results suggest that the specific assembly of Vps5-family SNX-BAR coats depends on inputs from unique N-terminal sequence features in addition to BAR domain coupling, expanding our understanding of endosomal coat assembly mechanisms.
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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) | 0.002 | 0.001 |
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".