TolC--the bacterial exit duct for proteins and drugs

FEBS Lett. 2003 Nov 27;555(1):66-71. doi: 10.1016/s0014-5793(03)01125-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / metabolism*
  • Biological Transport, Active
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Membrane Transport Proteins
  • Models, Molecular
  • Pharmaceutical Preparations / metabolism
  • Protein Conformation
  • Protein Structure, Secondary

Substances

  • Bacterial Outer Membrane Proteins
  • Escherichia coli Proteins
  • Membrane Transport Proteins
  • Pharmaceutical Preparations
  • tolC protein, E coli