TonB-dependent transporters: regulation, structure, and function

Annu Rev Microbiol. 2010;64:43-60. doi: 10.1146/annurev.micro.112408.134247.


TonB-dependent transporters (TBDTs) are bacterial outer membrane proteins that bind and transport ferric chelates, called siderophores, as well as vitamin B(12), nickel complexes, and carbohydrates. The transport process requires energy in the form of proton motive force and a complex of three inner membrane proteins, TonB-ExbB-ExbD, to transduce this energy to the outer membrane. The siderophore substrates range in complexity from simple small molecules such as citrate to large proteins such as serum transferrin and hemoglobin. Because iron uptake is vital for almost all bacteria, expression of TBDTs is regulated in a number of ways that include metal-dependent regulators, σ/anti-σ factor systems, small RNAs, and even a riboswitch. In recent years, many new structures of TBDTs have been solved in various states, resulting in a more complete understanding of siderophore selectivity and binding, signal transduction across the outer membrane, and interaction with the TonB-ExbB-ExbD complex. However, the transport mechanism is still unclear. In this review, we summarize recent progress in understanding regulation, structure, and function in TBDTs and questions remaining to be answered.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Biological Transport
  • Carbohydrate Metabolism
  • Energy Metabolism
  • Gene Expression Regulation, Bacterial*
  • Iron / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism*
  • Models, Biological
  • Nickel / metabolism
  • Proton-Motive Force
  • Siderophores / metabolism
  • Vitamin B 12 / metabolism


  • Bacterial Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Siderophores
  • tonB protein, Bacteria
  • Nickel
  • Iron
  • Vitamin B 12