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