An allosteric transport mechanism for the AcrAB-TolC Multidrug Efflux Pump

  1. Zhao Wang
  2. Guizhen Fan
  3. Corey F Hryc
  4. James N Blaza
  5. Irina I Serysheva
  6. Michael F Schmid
  7. Wah Chiu  Is a corresponding author
  8. Ben F Luisi  Is a corresponding author
  9. Dijun Du  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. The University of Texas Health Science Center at Houston Medical School, United States
  3. MRC Mitochondrial Biology Unit, United Kingdom
  4. University of Cambridge, United Kingdom

Abstract

Bacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics from the cell. In Gram-negative bacteria, some of these pumps form multi-protein assemblies that span the cell envelope. Here we report the near-atomic resolution cryoEM structures of the Escherichia coli AcrAB-TolC multidrug efflux pump in resting and drug transport states, revealing a quaternary structural switch that allosterically couples and synchronizes initial ligand binding with channel opening. Within the transport-activated state, the channel remains open even though the pump cycles through three distinct conformations. Collectively, our data provide a dynamic mechanism for the assembly and operation of the AcrAB-TolC pump.

Data availability

The following data sets were generated
    1. D. Du
    2. B.F. Luisi
    (2017) Crystal structure of AcrBZ complex: 2017
    Publicly available at PDB (accession no: 5NC5).

Article and author information

Author details

  1. Zhao Wang

    National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Guizhen Fan

    Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston Medical School, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Corey F Hryc

    National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. James N Blaza

    MRC Mitochondrial Biology Unit, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5420-2116
  5. Irina I Serysheva

    Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston Medical School, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael F Schmid

    National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Wah Chiu

    National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States
    For correspondence
    wah@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
  8. Ben F Luisi

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    bfl20@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1144-9877
  9. Dijun Du

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    dd339@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome

  • Ben F Luisi

Human Frontier Science Program

  • Ben F Luisi

National Institutes of Health (P41GM103832)

  • Wah Chiu

American Heart Association (16GRNT29720001)

  • Irina I Serysheva

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Olga Boudker, Weill Cornell Medical College, United States

Publication history

  1. Received: January 5, 2017
  2. Accepted: March 14, 2017
  3. Accepted Manuscript published: March 29, 2017 (version 1)
  4. Version of Record published: April 25, 2017 (version 2)

Copyright

© 2017, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Zhao Wang
  2. Guizhen Fan
  3. Corey F Hryc
  4. James N Blaza
  5. Irina I Serysheva
  6. Michael F Schmid
  7. Wah Chiu
  8. Ben F Luisi
  9. Dijun Du
(2017)
An allosteric transport mechanism for the AcrAB-TolC Multidrug Efflux Pump
eLife 6:e24905.
https://doi.org/10.7554/eLife.24905

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