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Multiple entry pathways within the efflux transporter AcrB contribute to multidrug recognition

Author

Listed:
  • Martijn Zwama

    (Osaka University
    Osaka University
    Osaka University)

  • Seiji Yamasaki

    (Osaka University)

  • Ryosuke Nakashima

    (Osaka University)

  • Keisuke Sakurai

    (Osaka University)

  • Kunihiko Nishino

    (Osaka University)

  • Akihito Yamaguchi

    (Osaka University)

Abstract

AcrB is the major multidrug exporter in Escherichia coli. Although several substrate-entrances have been identified, the specificity of these various transport paths remains unclear. Here we present evidence for a substrate channel (channel 3) from the central cavity of the AcrB trimer, which is connected directly to the deep pocket without first passing the switch-loop and the proximal pocket . Planar aromatic cations, such as ethidium, prefer channel 3 to channels 1 and 2. The efflux through channel 3 increases by targeted mutations and is not in competition with the export of drugs such as minocycline and erythromycin through channels 1 and 2. A switch-loop mutant, in which the pathway from the proximal to the deep pocket is hindered, can export only channel 3-utilizing drugs. The usage of multiple entrances thus contributes to the recognition and transport of a wide range of drugs with different physicochemical properties.

Suggested Citation

  • Martijn Zwama & Seiji Yamasaki & Ryosuke Nakashima & Keisuke Sakurai & Kunihiko Nishino & Akihito Yamaguchi, 2018. "Multiple entry pathways within the efflux transporter AcrB contribute to multidrug recognition," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02493-1
    DOI: 10.1038/s41467-017-02493-1
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