Replacement of helix 1′ enhances the lipid binding activity of apoE3 N‐terminal domain
Bibliographic record
Abstract
The N‐terminal domain of human apolipoprotein E3 (apoE3‐NT) harbors residues critical for interaction with members of the low‐density lipoprotein receptor (LDLR) family. While lipid free apoE3‐NT adopts a stable four‐helix bundle conformation, a lipid binding induced conformational adaptation is required for LDLR binding. To investigate the structural basis for this change, the short helix connecting helix 1 and 2 in the four helix bundle was replaced by the β‐turn sequence, ‐NPNG‐. Recombinant helix‐to‐turn (HT) variant apoE3‐NT was produced in E. coli , isolated and characterized. Stability studies revealed an unfolding transition midpoint of 1.9 M guanidine HCl for HT apoE3‐NT. Reconstituted HDL prepared with HT apoE3‐NT binds to the LDLR. HT apoE3‐NT was more effective than wild type apoE3‐NT at inducing a decrease in phospholipid vesicle light scattering intensity. In a competition binding experiment, HT apoE3‐NT preferentially associated with phospholipase C treated LDL. Results indicate that a mutation at one end of the apoE3‐NT four‐helix bundle markedly enhances the lipid binding activity of this protein. In full‐length apoE, increased NT domain lipid binding affinity may alter the ratio of receptor‐active and ‐inactive conformational states and influence lipoprotein‐LDLR interactions. Supported by TRDRP and NIH.
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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 | 0.000 |
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".