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TitleStructural mechanisms of pump assembly and drug transport in the AcrAB-TolC efflux system.
Journal, issue, pagesElife, Vol. 14, Year 2026
Publish dateApr 20, 2026
AuthorsXiaofei Ge / Zhiwei Gu / Jiawei Wang /
PubMed AbstractTripartite multidrug efflux pumps that span the cell envelope are essential for antibiotic resistance in Gram-negative bacteria. Here, we report cryo-EM structures of two endogenous efflux complexes ...Tripartite multidrug efflux pumps that span the cell envelope are essential for antibiotic resistance in Gram-negative bacteria. Here, we report cryo-EM structures of two endogenous efflux complexes from : a TolC-YbjP subcomplex at 3.56 Å resolution and the complete TolC-YbjP-AcrABZ pump at 3.39 Å. Structural analysis reveals that YbjP, a previously uncharacterized lipoprotein, binds TolC in a 3:3 stoichiometry, bridging the TolC protomers at their equatorial domain. Clear density of the mature YbjP's N-terminal Cys19 indicates that YbjP is anchored to the outer membrane by an N-terminal lipid moiety. Notably, YbjP remains bound as TolC undergoes AcrA-induced opening, suggesting that this accessory protein accommodates the conformational change. The AcrB trimer simultaneously presents three distinct conformational states (L, T, and O), capturing a complete transport cycle. These high-resolution structures provide insights into the architecture and mechanism of clinically relevant efflux machinery, identifying YbjP as a previously unrecognized structural component that contributes to TolC positioning, and may assist in its membrane localization.
External linksElife / PubMed:42007677 / PubMed Central
MethodsEM (single particle)
Resolution3.26 - 3.56 Å
Structure data

EMDB-64784, PDB-9v52:
Structure of TolC and YbjP closed state complex
Method: EM (single particle) / Resolution: 3.56 Å

EMDB-64785, PDB-9v53:
Structure of TolC, YbjP, and AcrABZ complex
Method: EM (single particle) / Resolution: 3.39 Å

EMDB-64787, PDB-9v55:
Structure of TolC, YbjP, and AcrA complex
Method: EM (single particle) / Resolution: 3.26 Å

Source
  • Escherichia coli (E. coli)
  • escherichia coli (strain k12) (bacteria)
  • escherichia coli k-12 (bacteria)
KeywordsPROTEIN TRANSPORT / Multidrug efflux pump / TolC / YbjP / AcrA / AcrB / lipoprotein / antibiotic resistance / Gram-negative

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