PROSITE documentation PDOC00354

TonB-dependent receptor (TBDR) proteins signatures and profile

In addition to a cytoplasmic membrane (CM), which is common to all organisms, Gram-negative bacteria possess an outer membrane (OM) that acts as a selective permeation barrier. TonB-dependent receptors (TBDRs) are transport proteins found at the OM to allow Gram-negative bacteria to uptake scarce resources from competitive environments with very high affinity. Early reports on TBDRs focused on the uptake of siderophore-iron complexes but recent studies have showed that the spectrum of ligands includes sugars, vitamins, heme, and other non-ferrous cations. All of them share the same basic architecture, a C-terminal membrane-embedded 22-strand antiparallel β-barrel domain that is sealed by a conserved N-terminal globular 'plug' domain (also called 'cork' or 'hatch') (see <PDB:3CSL>). The lengths of the extracellular loops from the plug and barrel domain are the main structural differences between the TBDRs. The extracellular loops are involved in transport. Their flexibility allows for the ligand recognition before binding into its binding pocket. TBDRs typically act as channels that open in response to outside ligands to allow import of extracellular nutrients into the periplasmic space. The TBDR-dependent substrate transport is an active process that requires energy input from the proton motive force across the cytoplasmic membrane. Such a process requires that the ligand-loaded TBDRs interact with the TonB protein complex consisting of three inner membrane proteins (TonB/ExbB/ExbD) (see <PDOC52015>. ExbB and ExbD are accessory proteins anchored in the CM that convey the pmf across the CM to TonB. TonB protein mediates the energy transduction from the CM to TBDRs [1,2,3,4,5,6,7]. The TonB protein also interacts with some colicins. The proteins that are currently known or presumed to interact with TonB are:

  Gene   Function or name
  ----   -------------------------------------------------------------------
  btuB   Receptor for cobalamin.
  cirA   Receptor for colicin I (exact substrate not known).
  fatA   Receptor for ferric anguibactin (Vibrio anguillarum).
  fcuA   Receptor for ferrichrome (Yersinia enterocolitica).
  fecA   Receptor for iron dicitrate.
  fepA   Receptor for ferrienterobactin (ferric enterochelin).
  fhuA   Receptor for ferrichrome-iron.
  fhuE   Receptor for ferric coprogen, ferrioxamine B, and rhodotrulic acid.
  foxA   Receptor for ferrioxamine (Yersinia enterocolitica).
  fptA   Receptor for Fe(III)-pyochelin (Pseudomonas aeruginosa).
  fpvA   Receptor for ferripyoverdine (Pseudomonas aeruginosa).
  fyuA   Receptor for pesticin and yersiniabactin (Yersinia).
  hemR   Receptor for hemin (Yersinia enterocolitica).
  hxuC   Receptor for heme/hemopexin (Haemophilus influenzae).
  irgA   Receptor for ferric vibriobactin (Vibrio cholerae).
  iroA   Receptor for a siderophore (Neisseria meningitidis).
  iutA   Receptor for ferric aerobactin.
  pbuA   Receptor for ferric pseudobactin M114 (Pseudomonas strain M114).
  pfeA   Receptor for ferric enterobactin (Pseudomonas aeruginosa).
  pupA   Receptor for ferric pseudobactin 358 (Pseudomonas putida).
  pupB   Receptor for ferric pseudobactin BN7 and BN8 (Pseudomonas putida).
  tbp1   Receptor for transferrin (Neisseria and Haemophilus).

  Haemophilus influenzae hypothetical proteins HI0262, HI0661, HI0635, HI0712,
  HI1217, and HI1567.

  cba    Colicin B, a channel forming colicin.
  cda    Colicin D.
  cma    Colicin M, inhibitor of murein biosynthesis.

Most of these proteins contain, at their N-terminus, a short conserved region [8,9,10], called the TonB-box, involved in the interaction of the protein with the TonB protein [11]. With the exception of the colicin B, D and M receptors they all also contain, in their C-terminal extremity a short conserved domain that contains two invariant residues. We also developed a profile that covers both the N-terminal plug domain and the C-terminal β-barrel domain.