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

eLife | 2017

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.

Pubmed ID: 28355133 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 200873/Z/16/Z
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM072804
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_14116
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM103832
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM079429
  • Agency: NLM NIH HHS, United States
    Id: T15 LM007093
  • Agency: NIH HHS, United States
    Id: S10 OD016279

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