MétaCan
Menu
Back to cohort
Record W2078356003 · doi:10.1074/jbc.m110.149179

Decoding Toxicity

2010· article· en· W2078356003 on OpenAlexaff
Wendy W. K. Mok, Nirav H. Patel, Yingfu Li

Bibliographic record

VenueJournal of Biological Chemistry · 2010
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBacterial Genetics and Biotechnology
Canadian institutionsMcMaster University
Fundersnot available
KeywordsBiologyPeptide sequenceAmino acidEscherichia coliPeptideGeneticsAntitoxinFunction (biology)MutantBiochemistryComputational biologyGeneToxin

Abstract

fetched live from OpenAlex

Bacterial genomes encode a collection of small peptides that are deleterious to their hosts when overexpressed. The physiological relevance of the majority of these peptides is unknown at present, although many of them have been implicated in regulatory processes important for cell survival and adaptability. One peptide that is of particular interest to us is a 19-amino acid proteic toxin, coined IbsC, whose production is repressed by SibC, an RNA antitoxin. Together, IbsC and SibC constitute a type I toxin-antitoxin (TA) pair. To better understand the function of IbsC and to decipher the sequence determinants for its toxic phenotype, we carried out extensive sequence analyses of the peptide. We generated a series of truncation and single amino acid deletion mutants to determine the minimal sequence required for toxicity. We further probed into functionally relevant amino acids with a comprehensive set of IbsC mutants produced using a systematic sequence randomization strategy. We found that IbsC remained toxic in the presence of multiple deletions and single amino acid substitutions, despite being well-conserved in Escherichia coli and across other Gram-negative bacteria. The toxicity of this peptide was determined to be dependent on a stretch of highly hydrophobic residues near its center. Our results defined sequence-function relationship of IbsC and offered additional insights into properties common to membrane-targeting type I toxins in E. coli and related species. Bacterial genomes encode a collection of small peptides that are deleterious to their hosts when overexpressed. The physiological relevance of the majority of these peptides is unknown at present, although many of them have been implicated in regulatory processes important for cell survival and adaptability. One peptide that is of particular interest to us is a 19-amino acid proteic toxin, coined IbsC, whose production is repressed by SibC, an RNA antitoxin. Together, IbsC and SibC constitute a type I toxin-antitoxin (TA) pair. To better understand the function of IbsC and to decipher the sequence determinants for its toxic phenotype, we carried out extensive sequence analyses of the peptide. We generated a series of truncation and single amino acid deletion mutants to determine the minimal sequence required for toxicity. We further probed into functionally relevant amino acids with a comprehensive set of IbsC mutants produced using a systematic sequence randomization strategy. We found that IbsC remained toxic in the presence of multiple deletions and single amino acid substitutions, despite being well-conserved in Escherichia coli and across other Gram-negative bacteria. The toxicity of this peptide was determined to be dependent on a stretch of highly hydrophobic residues near its center. Our results defined sequence-function relationship of IbsC and offered additional insights into properties common to membrane-targeting type I toxins in E. coli and related species.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.044
Threshold uncertainty score0.407

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.014
GPT teacher head0.246
Teacher spread0.233 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations25
Published2010
Admission routes1
Has abstractyes

Explore more

Same venueJournal of Biological ChemistrySame topicBacterial Genetics and BiotechnologyFrench-language works237,207