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Record W4413029591 · doi:10.1038/s41467-025-62604-1

Antimicrobial peptide class that forms discrete β-barrel stable pores anchored by transmembrane helices

2025· article· en· W4413029591 on OpenAlexafffund
Seth W. Dickey, Dylan J. Burgin, Ama N Antwi, Amer E. Villaruz, Madeline R. Galac, Gordon Y. C. Cheung, Tatiana K. Rostovtseva, L.J. Worrall, Aleksander C. Lazarski, Elio A. Cino, D. Peter Tieleman, Sergey M. Bezrukov, N.C.J. Strynadka, Michaël Otto

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicAntimicrobial Peptides and Activities
Canadian institutionsUniversity of CalgaryUniversity of British Columbia
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Mental HealthCanadian Institutes of Health ResearchAlliance de recherche numérique du CanadaUniversitair Medisch Centrum GroningenNational Institute of Child Health and Human DevelopmentUniversity of MarylandCanada Research ChairsNational Institutes of HealthU.S. Department of Health and Human ServicesGovernment of CanadaNational Institute of Allergy and Infectious DiseasesDivision of Intramural Research, National Institute of Allergy and Infectious Diseases
KeywordsAntimicrobial peptidesTransmembrane proteinBacteriocinMembrane topologyTransmembrane domainPeptideBiologyBacteriaMembrane proteinChemistryBiochemistryComputational biologyMembraneGeneticsReceptor

Abstract

fetched live from OpenAlex

Bacteriocin peptides are weapons of inter-bacterial warfare and belong to the larger group of antimicrobial peptides (AMPs), which are frequently proposed as alternatives to antibiotics. Many AMPs kill by destroying the target's cytoplasmic membrane using short-lived membrane perturbations. Contrastingly, protein toxins form large pores by stably assembling in the target membrane. Here we describe an AMP class termed TMcins (for transmembrane helix-containing bacteriocin), in which half of the AMP forms a transmembrane helix. This characteristic allows TMcin to assemble into stable and large oligomeric pores. The biosynthetic locus of TMcin, which was broadly active against Gram-positive bacteria, is distributed throughout two major bacterial phyla, yet bears no homology to previously reported bacteriocin biosynthetic gene clusters. Our discovery of an AMP class that achieves pore stability otherwise only found in protein toxins transforms our current understanding of AMP structure and function and underscores the continuing importance of phenotype-initiated investigations in uncovering wholly uncharacterized antimicrobials.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

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 head0.010
GPT teacher head0.264
Teacher spread0.254 · 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 source (direct Gemma or distilled Codex), 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

Citations10
Published2025
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicAntimicrobial Peptides and ActivitiesFrench-language works237,207