The role of proline in the membrane re‐entrant helix of caveolin‐1
Bibliographic record
Abstract
Caveolin‐1 (Cav1) has a segment of hydrophobic amino acids comprising approximately residues 103 to 122. We have performed an in silico analysis of the conformational preference of this segment of Cav1 using PepLook. We find that there is one main group of stable conformations corresponding to a hydrophobic U bent model that would not traverse the membrane. Furthermore, the calculations predict that substituting the Pro 110 residue with an Ala will change the conformation to a straight hydrophobic helix that would traverse the membrane. We have expressed the FLAG‐tagged P110A mutant of Cav1 in HEK 293 cells. We find that this mutation causes a large reduction of endocytosis of caveolae. We also evaluate the topology of the proteins with confocal immunofluorescence microscopy. The cells expressing Cav1 show that the hydrophobic segment of this protein is not transmembrane but takes up a bent conformation, making the protein monotopic. In contrast, the FLAG‐tagged P110A mutant is equally exposed to antibodies, before and after membrane permeabilization. Thus, the single Pro residue in the membrane‐inserting segment of Cav1 plays an important role in both the membrane topology of the protein as well as its function in the endocytosis of caveolin. (Supported by Canadian Post‐Doctoral Research Fellowships 2008–09 and by the Natural Sciences and Engineering Research Council of Canada, grant 9848)
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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 | 0.001 | 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".