Novel anionic cecropins from the spruce budworm feature a poly-L-aspartic acid C-terminus
Bibliographic record
Abstract
Abstract Cecropins form a family of amphipathic α-helical cationic peptides with broad-spectrum antibacterial properties and potent anticancer activity. The emergence of bacteria and cancer cells showing resistance to cationic antimicrobial peptides (CAMPs) has fostered a search for new, more selective and more effective alternatives to CAMPs. With this goal in mind, we looked for cecropin homologs in the genome and transcriptome of the spruce budworm, Choristoneura fumiferana . Not only did we find paralogs of the conventional cationic cecropins (Cfcec + ), our screening also led to the identification of previously uncharacterized anionic cecropins (Cfcec − ), featuring a poly-L-aspartic acid C-terminus. Comparative peptide analysis indicated that the C-terminal helix of Cfcec − is amphipathic, unlike that of Cfcec + , which is hydrophobic. Interestingly, molecular dynamics simulations pointed to the lower conformational flexibility of Cfcec − peptides, relative to that of Cfcec + . Phylogenetic analysis suggests that the evolution of distinct Cfcec + and Cfcec − peptides may have resulted from an ancient duplication event within the Lepidoptera. Our analyses also indicated that Cfcec − shares characteristics with entericidins, which are involved in bacterial programmed cell death, lunasin, a peptide of plant origins with antimitotic effects, and APC15, a subunit of the anaphase-promoting complex. Finally, we found that both anionic and cationic cecropins contain a BH3-like motif (G-[KQR]-[HKQNR]-[IV]-[KQR]) that could interact with Bcl-2, a protein involved in apoptosis; this observation is congruent with previous reports indicating that cecropins induce apoptosis. Altogether, our observations suggest that cecropins may provide templates for the development of new anticancer drugs. Graphical abstract Highlights Genes encoding novel anionic cecropins (Cfcec − ), featuring a C-terminal poly-L-aspartic acid, were found in the genome of the spruce budworm, Choristoneura fumiferana . Divergence between Cfcec + and Cfcec − could be the result of an ancient duplication event within the Lepidoptera. There is an apparent relationship between motifs observed in cecropin peptides and apoptosis. Anionic cecropins from the spruce budworm display characteristics suggesting they could have anticancer activity
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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) | 0.000 | 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 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".