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

Martijn Zwama, Seiji Yamasaki, Ryosuke Nakashima, Keisuke Sakurai, Kunihiko Nishino and Akihito Yamaguchi ()
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Martijn Zwama: Osaka University
Seiji Yamasaki: Osaka University
Ryosuke Nakashima: Osaka University
Keisuke Sakurai: Osaka University
Kunihiko Nishino: Osaka University
Akihito Yamaguchi: Osaka University

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02493-1

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