Hydrophobic Core of the Steroidogenic Acute Regulatory Protein for Cholesterol Transport
Bibliographic record
Abstract
The steroidogenic acute regulatory protein (StAR), the first family member of START (StAR-related lipid transport) proteins, plays an essential role by facilitating the movement of cholesterol from the outer to inner mitochondrial membrane. Wild-type and mutant StAR binds cholesterol with similar intensity, but only wild-type StAR can transport it to mitochondria. Here, we report that the hydrophobic core is crucial for biological activity of proteins with START domains. Wild-type StAR increased steroidogenic activity by 7-9-fold compared to mutant R182L StAR, but both of them showed similar near-UV CD spectra. The fluorescence maximum of wild-type StAR is red shifted in comparison to mutant StAR under identical urea concentration. TFE increased the alpha-helical contribution of wild-type StAR more than the mutant protein. Acrylamide quenching for the wild-type protein (K(SV) = 12.0 +/- 0.2-11.2 +/- 0.5 M(-1)) exceeded that of the mutant protein (K(SV) = 4 +/- 0.2 M(-1)). Consistent with these findings, the hydrophobic probe ANS bound wild-type StAR (K(app) = 8.1 x 10(5) M(-1)) to a greater degree than mutant StAR (K(app) = 3.75 x 10(5) M(-1)). Partial proteolysis examined by mass spectrometry suggests that only wild-type StAR has a protease-sensitive C-terminus, but not the mutant. Stopped-flow CD revealed that the time of unfolding of mutant StAR was 0.017 s. In contrast, the wild-type StAR protein is unfolded in 16.3 s. In summary, these results demonstrate that wild-type StAR adopts a very flexible form due to the accommodation of more water molecules, while mutant StAR is generated by an alternate folding pathway making it inactive.
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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 | 0.002 |
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".