title: Assembly and channel opening in a bacterial drug efflux machine.
abstract: Drugs and certain proteins are transported across the membranes of Gram-negative bacteria by energy-activated pumps. The outer membrane component of these pumps is a channel that opens from a sealed resting state during the transport process. We describe two crystal structures of the Escherichia coli outer membrane protein TolC in its partially open state. Opening is accompanied by the exposure of three shallow intraprotomer grooves in the TolC trimer, where our mutagenesis data identify a contact point with the periplasmic component of a drug efflux pump, AcrA. We suggest that the assembly of multidrug efflux pumps is accompanied by induced fit of TolC driven mainly by accommodation of the periplasmic component.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Vassiliy N
authors.initials: VN
authors.lastname: Bavro
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Pietras
authors.forename: Nicholas
authors.initials: N
authors.lastname: Furnham
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez-Cano
authors.forename: Juan
authors.initials: J
authors.lastname: Fernández-Recio
authors.forename: Xue Yuan
authors.initials: XY
authors.lastname: Pei
authors.forename: Rajeev
authors.initials: R
authors.lastname: Misra
authors.forename: Ben
authors.initials: B
authors.lastname: Luisi
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D018360:Crystallography, X-Ray; D004352:Drug Resistance, Microbial / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D011487:Protein Conformation
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083497:AcrA protein, E coli; C083496:AcrB protein, E coli; C073126:tolC protein, E coli