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Elife. 2017 Mar 29;6. pii: e24905. doi: 10.7554/eLife.24905.

An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump.

Author information

1
National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States.
2
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States.
3
Department of Biochemistry and Molecular Biology, Structural Biology Imaging Center, The University of Texas Health Science Center at Houston Medical School, Houston, United States.
4
Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, United States.
5
MRC Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom.
6
Department of Biochemistry, University of Cambridge, 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.

KEYWORDS:

AcrA; AcrZ; Carb; E. coli; TolC; biophysics; drug efflux; structural biology; tripartite assembly

PMID:
28355133
PMCID:
PMC5404916
DOI:
10.7554/eLife.24905
[Indexed for MEDLINE]
Free PMC Article

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