A model of a transmembrane drug-efflux pump from Gram-negative bacteria.
In Gram-negative bacteria, drug resistance is due in part to the activity of transmembrane efflux-pumps, which are composed of three types of proteins. A representative pump from Escherichia coli is an assembly of the trimeric outer-membrane protein TolC, which is an allosteric channel, the trimeric inner-membrane proton-antiporter AcrB, and the periplasmic protein, AcrA. The pump displaces drugs vectorially from the bacterium using proton electrochemical force. Crystal structures are available for TolC and AcrB from E. coli, and for the AcrA homologue MexA from Pseudomonas aeruginosa. Based on homology modelling and molecular docking, we show how AcrA, AcrB and TolC might assemble to form a tripartite pump, and how allostery may occur during transport.
Fernandez-Recio
Juan
J
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
Walas
Fabien
F
Federici
Luca
L
Venkatesh Pratap
J
J
Bavro
Vassiliy N
VN
Miguel
Ricardo Nunez
RN
Mizuguchi
Kenji
K
Luisi
Ben
B
D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D004352:Drug Resistance, Microbial; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011487:Protein Conformation
D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083496:AcrB protein, E coli; C118598:MexA protein, Pseudomonas aeruginosa; C073126:tolC protein, E coli