TolC - the bacterial exit duct for proteins and drugs

The ToIC structure has unveiled a common mechanism for the movement of molecules, large and small, from the bacterial cell cytosol, across two membranes and the intervening periplasm, into the environment. Trimeric ToIC is a remarkable cell exit duct that differs radically from other membrane proteins, comprising a 100-Angstrom long alpha-barrel that projects across the periplasmic space, anchored by a 40-Angstrom long beta-barrel spanning the outer membrane. The periplasmic entrance of ToIC is closed until recruitment by substrate-specific translocases in the inner membrane triggers its transition to the open state, achieved by an iris-like 'untwisting' of the tunnel alpha-helices. ToIC-dependent machineries present ubiquitous exit routes for virulence proteins and antibacterial drugs, and their conserved structure, specifically the electronegative ToIC entrance constriction, may present a target for inhibitors of multidrug-resistant pathogens. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.