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TitleStructure of the tripartite multidrug efflux pump AcrAB-TolC suggests an alternative assembly mode.
Journal, issue, pagesMol Cells, Vol. 38, Issue 2, Page 180-186, Year 2015
Publish dateJan 15, 2015
AuthorsJin-Sik Kim / Hyeongseop Jeong / Saemee Song / Hye-Yeon Kim / Kangseok Lee / Jaekyung Hyun / Nam-Chul Ha /
PubMed AbstractEscherichia coli AcrAB-TolC is a multidrug efflux pump that expels a wide range of toxic substrates. The dynamic nature of the binding or low affinity between the components has impeded elucidation ...Escherichia coli AcrAB-TolC is a multidrug efflux pump that expels a wide range of toxic substrates. The dynamic nature of the binding or low affinity between the components has impeded elucidation of how the three components assemble in the functional state. Here, we created fusion proteins composed of AcrB, a transmembrane linker, and two copies of AcrA. The fusion protein exhibited acridine pumping activity, suggesting that the protein reflects the functional structure in vivo. To discern the assembling mode with TolC, the AcrBA fusion protein was incubated with TolC or a chimeric protein containing the TolC aperture tip region. Three-dimensional structures of the complex proteins were determined through transmission electron microscopy. The overall structure exemplifies the adaptor bridging model, wherein the funnel-like AcrA hexamer forms an intermeshing cogwheel interaction with the α-barrel tip region of TolC, and a direct interaction between AcrB and TolC is not allowed. These observations provide a structural blueprint for understanding multidrug resistance in pathogenic Gram-negative bacteria.
External linksMol Cells / PubMed:26013259 / PubMed Central
MethodsEM (single particle)
Resolution24.0 - 26.0 Å
Structure data

EMDB-6317:
Three-dimensional structure of AcrAB-TolC complex
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-6318:
Three-dimensional structure of AcrAB and MacA-TolC alpha-hybrid dimer complex
Method: EM (single particle) / Resolution: 24.0 Å

Source
  • Escherichia coli (E. coli)

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