Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Science Policy Alerts

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 1 September 2006:
Vol. 313. no. 5791, pp. 1295 - 1298
DOI: 10.1126/science.1131542
Prev | Table of Contents | Next

Reports

Structural Asymmetry of AcrB Trimer Suggests a Peristaltic Pump Mechanism

Markus A. Seeger,1,3* André Schiefner,2*{dagger} Thomas Eicher,1 François Verrey,1 Kay Diederichs,2 Klaas M. Pos1{ddagger}

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.

1 Institute of Physiology and Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, Zürich, Switzerland.
2 Department of Biology, University of Konstanz, Universitätsstrasse 10, M647, D-78457 Konstanz, Germany.
3 Institute of Microbiology, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland.

* These authors contributed equally to this work.

{dagger} Present address: Department of Molecular Biology, BCC206, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

{ddagger} To whom correspondence should be addressed. E-mail: kmpos{at}access.unizh.ch

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Structure, Function, and Evolution of Bacterial ATP-Binding Cassette Systems.
A. L. Davidson, E. Dassa, C. Orelle, and J. Chen (2008)
Microbiol. Mol. Biol. Rev. 72, 317-364
   Abstract »    Full Text »    PDF »
The Key Residue for Substrate Transport (Glu14) in the EmrE Dimer Is Asymmetric.
I. Lehner, D. Basting, B. Meyer, W. Haase, T. Manolikas, C. Kaiser, M. Karas, and C. Glaubitz (2008)
J. Biol. Chem. 283, 3281-3288
   Abstract »    Full Text »    PDF »
Fitting Periplasmic Membrane Fusion Proteins to Inner Membrane Transporters: Mutations That Enable Escherichia coli AcrA To Function with Pseudomonas aeruginosa MexB.
G. Krishnamoorthy, E. B. Tikhonova, and H. I. Zgurskaya (2008)
J. Bacteriol. 190, 691-698
   Abstract »    Full Text »    PDF »
Site-Directed Disulfide Cross-Linking Shows that Cleft Flexibility in the Periplasmic Domain Is Needed for the Multidrug Efflux Pump AcrB of Escherichia coli.
Y. Takatsuka and H. Nikaido (2007)
J. Bacteriol. 189, 8677-8684
   Abstract »    Full Text »    PDF »
Assembly of the MexAB-OprM Multidrug Pump of Pseudomonas aeruginosa: Component Interactions Defined by the Study of Pump Mutant Suppressors.
D. Nehme and K. Poole (2007)
J. Bacteriol. 189, 6118-6127
   Abstract »    Full Text »    PDF »
Drug-Induced Conformational Changes in Multidrug Efflux Transporter AcrB from Haemophilus influenzae.
V. Dastidar, W. Mao, O. Lomovskaya, and H. I. Zgurskaya (2007)
J. Bacteriol. 189, 5550-5558
   Abstract »    Full Text »    PDF »
The yeast mitochondrial ADP/ATP carrier functions as a monomer in mitochondrial membranes.
L. Bamber, M. Harding, M. Monne, D.-J. Slotboom, and E. R. S. Kunji (2007)
PNAS 104, 10830-10834
   Abstract »    Full Text »    PDF »
Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response strategy.
A. Mahamoud, J. Chevalier, S. Alibert-Franco, W. V. Kern, and J.-M. Pages (2007)
J. Antimicrob. Chemother. 59, 1223-1229
   Abstract »    Full Text »    PDF »
A periplasmic coiled-coil interface underlying TolC recruitment and the assembly of bacterial drug efflux pumps.
S. Lobedanz, E. Bokma, M. F. Symmons, E. Koronakis, C. Hughes, and V. Koronakis (2007)
PNAS 104, 4612-4617
   Abstract »    Full Text »    PDF »
Substrate Competition Studies Using Whole-Cell Accumulation Assays with the Major Tripartite Multidrug Efflux Pumps of Escherichia coli.
C. A. Elkins and L. B. Mullis (2007)
Antimicrob. Agents Chemother. 51, 923-929
   Abstract »    Full Text »    PDF »
Highlights From The Literature.
(2006)
Physiology 21, 374-379
   Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)