title: Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism.
abstract: 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.
authors.affiliation: Institute of Physiology and Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, Zürich, Switzerland.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Seeger
authors.forename: André
authors.initials: A
authors.lastname: Schiefner
authors.forename: Thomas
authors.initials: T
authors.lastname: Eicher
authors.forename: François
authors.initials: F
authors.lastname: Verrey
authors.forename: Kay
authors.initials: K
authors.lastname: Diederichs
authors.forename: Klaas M
authors.initials: KM
authors.lastname: Pos
mesh_terms: D001692:Biological Transport; D003460:Crystallization; D018360:Crystallography, X-Ray; D004058:Diffusion; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000737:chemistry* / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons
chemical_list: D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011522:Protons; C083496:AcrB protein, E coli