The role of the TolC family in protein transport and multidrug efflux. From stereochemical certainty to mechanistic hypothesis.
Gram-negative bacteria are enveloped by a system of two membranes, and they use specialized multicomponent, energy-driven pumps to transport molecules directly across this double-layered partition from the cell interior to the extra-cellular environment. One component of these pumps is embedded in the outer-membrane, and the paradigm for its structure and function is the TolC protein from Escherichia coli. A common component of a wide variety of efflux pumps, TolC and its homologues are involved in the export of chemically diverse molecules ranging from large protein toxins, such as alpha-hemolysin, to small toxic compounds, such as antibiotics. TolC family members thus play important roles in conferring pathogenic bacteria with both virulence and multidrug resistance. These pumps assemble reversibly in a transient process that brings together TolC or its homologue, an inner-membrane-associated periplasmic component, an integral inner-membrane translocase and the substrate itself. TolC can associate in this fashion with a variety of different partners to participate in the transport of diverse substrates. We review here the structure and function of TolC and the other components of the efflux/transport pump.
Sharff
A
A
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
Fanutti
C
C
Shi
J
J
Calladine
C
C
Luisi
B
B
D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D001692:Biological Transport; D029968:Escherichia coli Proteins; D008561:Membrane Fusion; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011487:Protein Conformation; D021381:Protein Transport; D013237:Stereoisomerism
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; C073126:tolC protein, E coli