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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Allosteric Regulation
  • Anti-Bacterial Agents / metabolism*
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cryoelectron Microscopy
  • Escherichia coli / chemistry
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Protein Conformation

Substances

  • AcrAB-TolC protein, E coli
  • Anti-Bacterial Agents
  • Carrier Proteins
  • Escherichia coli Proteins