Studies of segmental isotope‐enriched apolipoprotein E3 N‐terminal domain
Bibliographic record
Abstract
Gene knock‐out and transgenic experiments in mice have revealed that apolipoprotein E (apoE) is critically involved in the homeostatic maintenance of blood cholesterol levels via a low density lipoprotein receptor(LDLR)‐mediated interaction. Although the lipid‐free structure of the apoE3 N‐terminal (NT) region has been structurally well characterized, the lipid induced conformational change within the NT α‐helical region is less defined. In an attempt to further characterize the nature of the lipidated apoE3 NT helix 4 within the context of the native NT domain, a protein segmental isotopic labeling method was employed to study the protein using heteronuclear multidimensional NMR spectroscopy. A fusion protein comprised of a chitin binding domain, a Saccharomyces cerevisae intein domain and apoE NT residues 1‐111 was expressed and the apoE fragment was released from the column by a 2‐mercaptoethanesulfonic acid (MESNA)‐induced cleavage. ApoE3 NT 112‐183 fusion protein was expressed in 15 N and/or 13 C‐ enriched minimal media and isolated via a pH and temperature induced succinimide formation resulting in polypeptide chain cleavage. HPLC purified apoE3(1‐111) and apoE3(112‐183) proteins were ligated to generate the intact apoE3 NT segmentally‐labeled protein. Studies of this segmentally labeled protein provide insight into the mechanism of apoE‐LDLR interaction.
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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".