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| Title | Structural mechanisms of pump assembly and drug transport in the AcrAB-TolC efflux system. |
|---|---|
| Journal, issue, pages | Elife, Vol. 14, Year 2026 |
| Publish date | Apr 20, 2026 |
Authors | Xiaofei Ge / Zhiwei Gu / Jiawei Wang / ![]() |
| PubMed Abstract | 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 ...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 links | Elife / PubMed:42007677 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.26 - 3.56 Å |
| Structure data | EMDB-64784, PDB-9v52: EMDB-64785, PDB-9v53: EMDB-64787, PDB-9v55: |
| Source |
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Keywords | PROTEIN TRANSPORT / Multidrug efflux pump / TolC / YbjP / AcrA / AcrB / lipoprotein / antibiotic resistance / Gram-negative |
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