Structural and functional aspects of the multidrug efflux pump AcrB

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• The AcrA/AcrB/TolC system is the primary multidrug efflux pump in Escherichia coli.
• AcrB, the inner membrane transporter, is crucial for substrate recognition and energy transduction.
• It functions as a proton/drug antiporter, contributing to bacterial resistance.

Purpose of the Study:

• To elucidate the functional mechanism of the AcrB transporter.
• To understand how conformational changes facilitate drug efflux.
• To investigate the role of substrate binding pockets in transport.

Main Methods:

• Analysis of recent structural studies of homotrimeric AcrB.
• Examination of different monomer conformations.
• Inference of transport cycle intermediates.

Main Results:

• Homotrimeric AcrB adopts distinct monomer conformations during an allosteric functional rotation transport cycle.
• These conformational changes generate an alternate access drug transport tunnel.
• A hydrophobic substrate binding pocket is identified within an intermediate state of the cycle.

Conclusions:

• The findings reveal a dynamic transport mechanism for AcrB.
• Conformational rotation is key to the function of this major bacterial efflux pump.
• Understanding this mechanism can inform strategies to overcome antibiotic resistance.