An allosteric transport mechanism for the AcrAB-TolC Multidrug Efflux Pump
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
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Crystal structure of AcrBZ complex: 2017Publicly available at PDB (accession no: 5NC5).
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The apo structure of AcrAB-TolC tripartite multidrug efflux pump: 2017Publicly available at EBI Protein Data Bank (accession no: EMD-8636).
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The asymmetric structure of AcrAB-TolC tripartite multidrug efflux pump: 2017Publicly available at EBI Protein Data Bank (accession no: EMD-8640).
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The symmetric structure of AcrAB-TolC tripartite multidrug efflux pump with inhibitor MBX3132 bound: 2017Publicly available at EBI Protein Data Bank (accession no: EMD-3636).
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The apo structure of AcrAB-TolC tripartite multidrug efflux pump: 2017Publicly available at PDB (accession no: 5V5S).
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The asymmetric structure of AcrAB-TolC tripartite multidrug efflux pump: 2017Publicly available at PDB (accession no: 5V78).
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The symmetric structure of AcrAB-TolC tripartite multidrug efflux pump with inhibitor MBX3132 bound: 2017Publicly available at PDB (accession no: 5NG5).
Article and author information
Author details
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
- Olga Boudker, Weill Cornell Medical College, United States
Version history
- Received: January 5, 2017
- Accepted: March 14, 2017
- Accepted Manuscript published: March 29, 2017 (version 1)
- 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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