Structural Asymmetry of AcrB Trimer Suggests a Peristaltic Pump Mechanism
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Open Access
- 1 September 2006
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 313 (5791) , 1295-1298
- https://doi.org/10.1126/science.1131542
Abstract
The AcrA/AcrB/TolC complex spans the inner and outer membranes of Escherichia coli and serves as its major drug-resistance pump. Driven by the proton motive force, it mediates the efflux of bile salts, detergents, organic solvents, and many structurally unrelated antibiotics. Here, we report a crystallographic structure of trimeric AcrB determined at 2.9 and 3.0 angstrom resolution in space groups that allow asymmetry of the monomers. This structure reveals three different monomer conformations representing consecutive states in a transport cycle. The structural data imply an alternating access mechanism and a novel peristaltic mode of drug transport by this type of transporter.Keywords
This publication has 33 references indexed in Scilit:
- Structural evidence for induced fit and a mechanism for sugar/H+ symport in LacYThe EMBO Journal, 2006
- Interaction of the MexA and MexB Components of the MexAB-OprM Multidrug Efflux System of Pseudomonas aeruginosa : Identification of MexA Extragenic Suppressors of a T578I Mutation in MexBAntimicrobial Agents and Chemotherapy, 2005
- Direct Interaction of Multidrug Efflux Transporter AcrB and Outer Membrane Channel TolC Detected via Site-Directed Disulfide Cross-LinkingBiochemistry, 2005
- Crystallographic analysis of AcrBFEBS Letters, 2004
- Extramembrane Central Pore of Multidrug Exporter AcrB in Escherichia coli Plays an Important Role in Drug TransportJournal of Biological Chemistry, 2004
- X-ray diffraction of bacteriorhodopsin photocycle intermediates (Review)Molecular Membrane Biology, 2004
- Structure and Mechanism of the Lactose Permease of Escherichia coliScience, 2003
- Structural Basis of Multiple Drug-Binding Capacity of the AcrB Multidrug Efflux PumpScience, 2003
- Identification of Essential Charged Residues in Transmembrane Segments of the Multidrug Transporter MexB of Pseudomonas aeruginosaJournal of Bacteriology, 2001
- The Accessibility of a Novel Reentrant Loop of the Glutamate Transporter GLT-1 Is Restricted by Its SubstratePublished by Elsevier ,2000