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Record W4391681169 · doi:10.1038/s41564-024-01603-2

Synthesis of lipid-linked precursors of the bacterial cell wall is governed by a feedback control mechanism in Pseudomonas aeruginosa

2024· article· en· W4391681169 on OpenAlexafffund
Lindsey S. Marmont, Anna K. Orta, Becca W A Baileeves, David Sychantha, Ana Fernández-Galliano, Yancheng E. Li, Neil G. Greene, Robin A. Corey, Phillip J. Stansfeld, William Clemons, Thomas G. Bernhardt

Bibliographic record

VenueNature Microbiology · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBacterial Genetics and Biotechnology
Canadian institutionsMcMaster University
FundersNational Institute of General Medical SciencesBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research CouncilNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchUniversity of WarwickResearch Councils UKCanadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of CanadaG. Harold and Leila Y. Mathers FoundationUniversities Space Research AssociationWellcome TrustNational Institute of Allergy and Infectious DiseasesMedical Research CouncilHoward Hughes Medical InstituteCalifornia Institute of TechnologyDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesMcMaster UniversityNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsPeptidoglycanLipid IIPseudomonas aeruginosaBiogenesisLipid AExtracellularEnzymeChemistryGlycanCell biologyBiochemistryDimerCell wallBacterial cell structureMonomerBacteriaBiophysicsBiologyGeneGlycoproteinGenetics

Abstract

fetched live from OpenAlex

Many bacterial surface glycans such as the peptidoglycan (PG) cell wall are built from monomeric units linked to a polyprenyl lipid carrier. How this limiting carrier is distributed among competing pathways has remained unclear. Here we describe the isolation of hyperactive variants of Pseudomonas aeruginosa MraY, the enzyme that forms the first lipid-linked PG precursor. These variants result in the elevated production of the final PG precursor lipid II in cells and are hyperactive in vitro. The activated MraY variants have substitutions that map to a cavity on the extracellular side of the dimer interface, far from the active site. Our structural and molecular dynamics results suggest that this cavity is a binding site for externalized lipid II. Overall, our results support a model in which excess externalized lipid II allosterically inhibits MraY, providing a feedback mechanism that prevents the sequestration of lipid carrier in the PG biogenesis pathway.

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 categoriesResearch integrity
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 score0.067
Threshold uncertainty score0.999

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 science0.0010.000
Research integrity0.0020.000
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 head0.002
GPT teacher head0.189
Teacher spread0.187 · 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.

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

Citations11
Published2024
Admission routes2
Has abstractyes

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