Structural Asymmetry of AcrB Trimer Suggests a Peristaltic Pump Mechanism

• Published in: Science (American Association for the Advancement of Science) Vol. 313; no. 5791; pp. 1295 - 1298
• Main Authors: Seeger, Markus A, Schiefner, André, Eicher, Thomas, Verrey, François, Diederichs, Kay, Pos, Klaas M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 01.09.2006; The American Association for the Advancement of Science
• Subjects: Biological and medical sciences; Biological Transport; Crystal structure; Crystalline structure; Crystallization; Crystallography; Crystallography, X-Ray; Crystals; Diffusion; Drug resistance; Drug Resistance, Multiple, Bacterial; E coli; Escherichia coli; Escherichia coli - chemistry; Escherichia coli - drug effects; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Geometric planes; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - metabolism; Models, Molecular; Molecular biophysics; Monomers; Multidrug Resistance-Associated Proteins - chemistry; Multidrug Resistance-Associated Proteins - metabolism; Pharmacology; Protein Conformation; Protein Structure, Quaternary; Protein Structure, Secondary; Protein Structure, Tertiary; Protons; Pumps; Solutes; Spermatozoa; Structure in molecular biology; Trimers; Tunnels; Trimer; Peristaltic pump; Three dimensional structure; Escherichia coli; Bacteria; Mechanism; Enterobacteriaceae; Crystalline structure
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1131542

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.