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

DOI: 10.7554/eLife.24905 DOI Help

Authors: Zhao Wang (Baylor College of Medicine) , Guizhen Fan (The University of Texas Health Science Center at Houston Medical School) , Corey F Hryc (Baylor College of Medicine) , James N. Blaza (MRC Mitochondrial Biology Unit) , Irina I. Serysheva (The University of Texas Health Science Center at Houston Medical School) , Michael F Schmid (Baylor College of Medicine) , Wah Chiu (Baylor College of Medicine) , Ben Luisi (University of Cambridge) , Dijun Du (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 6

State: Published (Approved)
Published: March 2017
Diamond Proposal Number(s): 14043

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

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