Structure and function of TolC: the bacterial exit duct for proteins and drugs

Annu Rev Biochem. 2004;73:467-89. doi: 10.1146/annurev.biochem.73.011303.074104.


The bacterial TolC protein plays a common role in the expulsion of diverse molecules, which include protein toxins and antibacterial drugs, from the cell. TolC is a trimeric 12-stranded alpha/beta barrel, comprising an alpha-helical trans-periplasmic tunnel embedded in the outer membrane by a contiguous beta-barrel channel. This structure establishes a 140 A long single pore fundamentally different to other membrane proteins and presents an exit duct to substrates, large and small, engaged at specific inner membrane translocases. TolC is open to the outside medium but is closed at its periplasmic entrance. When TolC is recruited by a substrate-laden translocase, the entrance is opened to allow substrate passage through a contiguous machinery spanning the entire cell envelope, from the cytosol to the external environment. Transition to the transient open state is achieved by an iris-like mechanism in which entrance alpha-helices undergo an untwisting realignment, thought to be stabilized by interaction with periplasmic helices of the translocase. TolC family proteins are ubiquitous among gram-negative bacteria, and the conserved entrance aperture presents a possible cheomotherapeutic target in multidrug-resistant pathogens.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Biological Transport, Active
  • Escherichia coli Proteins
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / metabolism
  • Membrane Transport Proteins
  • Models, Molecular
  • Phylogeny
  • Protein Conformation
  • Proteins / metabolism
  • Toxins, Biological / metabolism


  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Escherichia coli Proteins
  • Membrane Transport Proteins
  • Proteins
  • Toxins, Biological
  • tolC protein, E coli