title: TolC--the bacterial exit duct for proteins and drugs.
abstract: The TolC 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 TolC is a remarkable cell exit duct that differs radically from other membrane proteins, comprising a 100-A long alpha-barrel that projects across the periplasmic space, anchored by a 40-A long beta-barrel spanning the outer membrane. The periplasmic entrance of TolC 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. TolC-dependent machineries present ubiquitous exit routes for virulence proteins and antibacterial drugs, and their conserved structure, specifically the electronegative TolC entrance constriction, may present a target for inhibitors of multidrug-resistant pathogens.
authors: Cambridge University Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK. vk103@mole.bio.cam.ac.uk
authors: Vassilis
authors: V
authors: Koronakis
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D001693:Biological Transport, Active; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; C073126:tolC protein, E coli