An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump
Zhao Wang,
Guizhen Fan,
Corey F Hryc,
James N Blaza,
Irina I Serysheva,
Michael F Schmid,
Wah Chiu,
Ben F Luisi,
Dijun Du
Affiliations
Zhao Wang
National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States
Guizhen Fan
Department of Biochemistry and Molecular Biology, Structural Biology Imaging Center, The University of Texas Health Science Center at Houston Medical School, Houston, United States
National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States; Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, United States
MRC Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge, United Kingdom
Irina I Serysheva
Department of Biochemistry and Molecular Biology, Structural Biology Imaging Center, The University of Texas Health Science Center at Houston Medical School, Houston, United States
Michael F Schmid
National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States
Wah Chiu
National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, United States; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, United States; Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, United States
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.
