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Record W7117248934 · doi:10.64898/2025.12.22.696046

YfgH is a transmembrane glycine-zipper containing lipoprotein that stabilizes excess cardiolipin and outer membrane proteins during envelope stress

2025· article· W7117248934 on OpenAlexafffund
Ethan RM Shaigec, Timothy Hyun Seok Cho, Valeria Tsviklist, Justin Bishop, Tracy Raivio

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typearticle
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicBacterial Genetics and Biotechnology
Canadian institutionsUniversity of Alberta
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchUniversities Space Research Association
KeywordsBacterial outer membraneBiogenesisTransmembrane proteinCardiolipinMembrane proteinTransmembrane domainMembraneLipid bilayerCell envelope

Abstract

fetched live from OpenAlex

ABSTRACT The outer membrane (OM) of Escherichia coli is an essential, asymmetric bilayer composed of lipopolysaccharide and phospholipids that protects cells from environmental stress. While several systems maintain OM integrity during stress, the roles of many outer membrane lipoproteins are less well characterized. Here, we identify YfgH, a glycine-zipper domain containing lipoprotein, as a novel OM-stabilizing factor that functions distinctly from the previously studied SlyB. Deletion of yfgH increases sensitivity to detergents and metal chelators, enhances OM permeability, and leads to global loss of OM proteins under stress. YfgH is essential for survival during CRISPR interference-mediated depletion of OM biogenesis genes, and its overexpression rescues these phenotypes. AlphaFold modeling predicts YfgH forms oligomeric ring-like structures similar to SlyB, but genetic suppressor screens indicate distinct mechanisms: clsA (cardiolipin synthase) mutations suppress yfgH deletion, while slyB suppressors map to the Mla lipid transport pathway. Biochemical analyses reveal YfgH interacts with multiple OM proteins, especially under stress. Together these findings suggest YfgH functions by stabilizing cardiolipin-rich nanodomains, representing a novel response to OM stress. This work expands our understanding of glycine-zipper lipoproteins as stress-specific membrane stabilizers and highlights the critical role of YfgH in preserving OM integrity during envelope perturbation. Importance The bacterial outer membrane is essential for survival in harsh environments, yet how Gram-negative cells maintain its stability under stress remains less understood. We identify YfgH, a previously uncharacterized outer membrane lipoprotein, as a key factor that preserves membrane integrity during envelope stress. Our findings show that YfgH stabilizes cardiolipin-rich nanodomains and protects outer membrane proteins when biogenesis pathways are compromised. This work reveals a new mechanism of outer membrane maintenance and expands the functional repertoire of glycine zipper– containing lipoproteins, highlighting a broader family of stress-specific membrane stabilizers that may be conserved across Gram-negative bacteria.

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 score0.000
Threshold uncertainty score0.002

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)0.0000.000

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 head0.007
GPT teacher head0.202
Teacher spread0.195 · 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

Citations0
Published2025
Admission routes2
Has abstractyes

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