Abstract
AcrB is a principal multidrug efflux transporter in Escherichia coli that cooperates with an outer-membrane channel, TolC, and a membrane-fusion protein, AcrA. Here we describe crystal structures of AcrB with and without substrates. The AcrB-drug complex consists of three protomers, each of which has a different conformation corresponding to one of the three functional states of the transport cycle. Bound substrate was found in the periplasmic domain of one of the three protomers. The voluminous binding pocket is aromatic and allows multi-site binding. The structures indicate that drugs are exported by a three-step functionally rotating mechanism in which substrates undergo ordered binding change.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacterial Outer Membrane Proteins / metabolism
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Binding Sites
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Cell Membrane / metabolism
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Crystallography, X-Ray
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Escherichia coli / chemistry
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Escherichia coli Proteins / chemistry*
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Escherichia coli Proteins / metabolism*
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Lipoproteins / metabolism
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Membrane Transport Proteins
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Minocycline / chemistry
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Minocycline / metabolism
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Models, Biological*
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Models, Molecular
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Multidrug Resistance-Associated Proteins / chemistry*
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Multidrug Resistance-Associated Proteins / metabolism*
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Rotation*
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Structure-Activity Relationship
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Substrate Specificity
Substances
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AcrA protein, E coli
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AcrB protein, E coli
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Bacterial Outer Membrane Proteins
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Escherichia coli Proteins
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Lipoproteins
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Membrane Transport Proteins
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Multidrug Resistance-Associated Proteins
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tolC protein, E coli
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Minocycline
Associated data
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PDB/2DHH
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PDB/2DR6
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PDB/2DRD