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Updated: Jul 3, 2026
13:40
In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
Published on: February 17, 2014
Multidrug efflux transporter, AcrB--the pumping mechanism
1Department of Life Science, Tokyo Institute of Technology, Nagatsuta, Yokohama, Japan. murakami@bio.titech.ac.jp
Current Opinion in Structural Biology
|July 23, 2008
Summary
Resistance nodulation cell division (RND) transporters, like E. coli AcrB, drive bacterial multidrug resistance by pumping antibiotics out of cells. Structural studies reveal their asymmetric trimer form and a unique transport mechanism involving functional rotation.
Area of Science:
- Bacteriology
- Structural Biology
- Biochemistry
Background:
- Resistance nodulation cell division (RND) transporters are key contributors to bacterial multidrug resistance.
- These transporters expel a broad spectrum of antibiotics from bacterial cells using proton motive force.
- AcrB is the primary RND transporter identified in Escherichia coli.
Purpose of the Study:
- To elucidate the structural basis of AcrB's function in antibiotic efflux.
- To understand the transport mechanism of RND transporters at a molecular level.
- To compare the transport pathway of RND transporters with other major transporter families.
Main Methods:
- Determination of crystal structures of the AcrB transporter from Escherichia coli.
- Analysis of multiple crystal structures obtained from different space groups.
- Comparative analysis of structural features with ATP binding cassette (ABC) and major facilitator superfamily (MFS) transporters.
Main Results:
- Acquired crystal structures consistently depict AcrB as an asymmetric trimer.
- Each monomer adopts a distinct conformation, representing different states within the transport cycle.
- Hydrophobic drugs were observed bound within the periplasmic domain of one monomer.
- The transport pathway, utilizing an alternating access mechanism, is located in the periplasmic hydrophilic domain, distinct from membrane-embedded pathways in ABC and MFS transporters.
- Protonation is suggested to occur asymmetrically at charged residues in the transmembrane region.
- Drug transport is facilitated by a three-step functional rotation involving ordered substrate binding changes.
Conclusions:
- The asymmetric trimeric structure of AcrB is crucial for its function in multidrug resistance.
- RND transporters possess a unique transport mechanism with a periplasmic pathway, differing from other transporter families.
- Structural insights support a model of drug transport via ordered binding changes and functional rotation within the AcrB trimer.
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