The structure and mechanism of the TolC outer membrane transport protein

Gram-negative bacteria have evolved specialized multicomponent systems that transport molecules from the cytoplasm to the extracellular environment in energydependent processes. Central to one of these systems is the TolC family of outer membrane proteins. TolC of Escherichia coli is a very versatile channel that can interact with a wide range of inner membrane, energydriven pumps to export compounds ranging from small antibiotic molecules to large toxic proteins. Thus TolC and its associated partner proteins confer invasive virulence and drug resistance to Gram-negative bacterial pathogens. However TolC is also a source of vulnerability, as it is a conduit for the uptake of bactericidal proteins known as colicins. Recently the crystal structures have been reported of TolC and its inner-membrane partner protein AcrB, a proton antiporter. The mechanisms of colicin uptake via TolC have also been extensively studied and the structures of some of the implicated protein components have been determined. In this review we focus on the current understanding of the structure and function relationships in TolC-mediated transport systems.