Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors
2007

Understanding the Drug Export Mechanism of E. Coli's AcrB

publication Evidence: high

Author Information

Author(s): Gaby Sennhauser, Patrick Amstutz, Christophe Briand, Otso Storchenegger, Markus G. Grütter

Primary Institution: Department of Biochemistry, University of Zurich, Zurich, Switzerland

Hypothesis

How does the multidrug exporter AcrB in E. coli facilitate drug efflux?

Conclusion

The study reveals that AcrB operates through distinct channels in each of its subunits, which are crucial for its drug export mechanism.

Supporting Evidence

  • The crystal structure of AcrB was determined at 2.5-Å resolution.
  • Each of the three AcrB subunits exhibited different conformations.
  • The study provides insights into how proton motive force is used for drug export.

Takeaway

AcrB is like a tiny pump in bacteria that helps them get rid of harmful drugs. This study shows how it works by using special proteins to see inside it.

Methodology

The researchers used designed ankyrin-repeat proteins (DARPins) to stabilize and study the AcrB protein's structure through crystallization.

Limitations

The exact inhibition mechanism of the DARPins on AcrB is not fully understood.

Digital Object Identifier (DOI)

10.1371/journal.pbio.0050007

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