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Crystal structure of bacterial multidrug efflux transporter AcrB


AcrB is a major multidrug exporter in Escherichia coli. It cooperates with a membrane fusion protein, AcrA, and an outer membrane channel, TolC. We have determined the crystal structure of AcrB at 3.5 Å resolution. Three AcrB protomers are organized as a homotrimer in the shape of a jellyfish. Each protomer is composed of a transmembrane region 50 Å thick and a 70 Å protruding headpiece. The top of the headpiece opens like a funnel, where TolC might directly dock into AcrB. A pore formed by three α-helices connects the funnel with a central cavity located at the bottom of the headpiece. The cavity has three vestibules at the side of the headpiece which lead into the periplasm. In the transmembrane region, each protomer has twelve transmembrane α-helices. The structure implies that substrates translocated from the cell interior through the transmembrane region and from the periplasm through the vestibules are collected in the central cavity and then actively transported through the pore into the TolC tunnel.

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We thank T. Tsukihara for advice on all stages of our X-ray crystallographic analysis and critical reading of this manuscript, and M. Yoshida, H. Nikaido and E. Bibi for critical reading and discussions. We are also grateful to A. Nakagawa, M. Kusunoki and G. Kurisu for help in the diffraction data collection and computation. We thank D. Goodhew-Davison for English correction. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. This work was done with the approval of the Joint Research Committee of Institute for Protein Research, Osaka University.

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Correspondence to Akihito Yamaguchi.

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Figure 1: Stereo view of the experimental electron density map (2.0σ contoured, purple) of the AcrB protomer at 3.5 Å resolution.
Figure 2: Structure of AcrB.
Figure 3: The structure of a single protomer.
Figure 4: A cutaway stereo view displaying the solvent-accessible surface of AcrB rendered with GRASP45.
Figure 5: Proposed model of the AcrB–AcrA–TolC complex and the schematic mechanism of multidrug export mediated by AcrAB-TolC system.


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