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TitleStructural basis of cooperative neutralization of the PldB toxin by immunity proteins in Pseudomonas aeruginosa.
Journal, issue, pagesCommun Biol, Year 2026
Publish dateJul 14, 2026
AuthorsXiaoyun Yang / Jiawen Yang / Hong Wang / Xiuhua Liu / Zongqiang Li /
PubMed AbstractPldB, a type VI secretion system-dependent phospholipase D (PLD) effector secreted by multidrug-resistant Pseudomonas aeruginosa, alters host cell membrane permeability and facilitates pathogen ...PldB, a type VI secretion system-dependent phospholipase D (PLD) effector secreted by multidrug-resistant Pseudomonas aeruginosa, alters host cell membrane permeability and facilitates pathogen internalization. Its cytotoxic activity is neutralized by three cognate immunity proteins-PA5086, PA5087, and PA5088-which protect the bacterium from self-intoxication. However, the underlying mechanism remains unclear. Through quantitative and qualitative analyses, we demonstrate that these three immunity proteins function cooperatively to inhibit PldB toxicity. Cryogenic electron microscopy of the PldB-PA5088 complex reveals that PA5088 binds to the HKD2 domain of PldB primarily through electrostatic interactions, markedly reducing the volume of its active center. Interaction studies using domain‑specific truncated PldB variants, together with enzyme activity assays, identify distinct copy numbers and binding regions for PA5086, PA5087, and PA5088 in their association with PldB. Collectively, our findings provide mechanistic insights into immunity protein-mediated neutralization of PldB toxicity, offering a potential foundation for designing PLD-targeting therapeutics against P. aeruginosa infection.
External linksCommun Biol / PubMed:42448982
MethodsEM (single particle)
Resolution3.56 - 3.59 Å
Structure data

67105

9xq9

EMDB-67105, PDB-9xq9:
The structure of PldB-PA5088 complex state_1
Method: EM (single particle) / Resolution: 3.59 Å

67118

9xqm

EMDB-67118, PDB-9xqm:
The structure of PldB-PA5088 complex state_2
Method: EM (single particle) / Resolution: 3.56 Å

Source
  • pseudomonas aeruginosa (bacteria)
KeywordsIMMUNE SYSTEM / Inhibitor / Complex

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