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PDB:1IWG

Protein Name

Multidrug efflux transporter AcrB

Species

Escherichia coli (bacteria)

Biological Context

Antibiotics are frequently used for the treatment of various infectious diseases. Their overuse, however, has been increasingly causing the big problem of drug resistance. In order to protect themselves, bacteria expel various drugs which are noxious for them. This process is one of the ways through which bacteria gain multidrug resistance. The common antibiotics become ineffective for the treatment of infectious diseases caused by bacteria that have acquired such resistance. Recent discovery of bacteria resistant for vancomycin, which is regarded as the most efficient antibiotics, as well as of a tubercle bacillus with drug resistance has raised the concern even more. The multidrug exporter proteins concern the multidrug resistances of bacteria. The AcrAB-TolC system of Escherichia coli is an example and includes some multidrug exporter proteins with functions for multidrug efflux. In bacteria, two cell membranes and the periplasm, the region between the two membranes, separate the inside of the cell from the outside. The AcrAB-TolC system consists mainly of AcrB which passes through the inner membrane and continues into the periplasm, TolC which passes through the outer membrane from the periplasm and extends to the outside of the cell, and AcrA which is located in the periplasm and connects the two membranes.

Structure Description

1iwg1iwg_x1iwg_y

The three-dimensional structure of AcrB has been determined. AcrB is a homotrimer and is composed of a transmembrane region and a headpiece protruding to the periplasm. Three subunits form the pore which allows the passage of various substrates. The top of the headpiece is shaped like a funnel, at which AcrB binds to TolC. TolC, whose structure has also been determined (see xPSSS:1EK9xPSSS:1TQQ), is a homotrimer and consists of a long cylinder and a channel which passes through the outer membrane. When a substrate such as drugs exported from the inside of the cell contacts with AcrAB, AcrAB and TolC form a transient complex and export it to the outside of the cell. Thus this system is active in the efflux of various substrates, e.g. negative and positive ions and neutral compounds. The structure determination of AcrB has provided a clearer understanding for the mechanisms of the multidrug efflux and for the ways in which multidrug resistance is generated.

Protein Data Bank (PDB)

References

Source

Murakami, S. Nakashima, R. Yamashita, E. Yamaguchi, A.; "Crystal structure of bacterial multidrug efflux transporter AcrB"; NATURE; (2002) 419:587-593 PubMed:12374972.

Others

UniProt:P31224

author: Yuko Tsuchiya


Japanese version:PDB:1IWG