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.

Last update:

January 2023 / Text revised; profile added.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

TONB_DEPENDENT_REC_3, PS52016; TonB-dependent receptor (TBDR) proteins profile  (MATRIX)

TONB_DEPENDENT_REC_1, PS00430; TonB-dependent receptor (TBDR) proteins signature 1  (PATTERN)

TONB_DEPENDENT_REC_2, PS01156; TonB-dependent receptor (TBDR) proteins signature 2  (PATTERN)


1AuthorsLim B.L.
TitleTonB-dependent receptors in nitrogen-fixing nodulating bacteria.
SourceMicrobes. Environ. 25:67-74(2010).
PubMed ID21576856

2Authorsde Amorim G.C. Prochnicka-Chalufour A. Delepelaire P. Lefevre J. Simenel C. Wandersman C. Delepierre M. Izadi-Pruneyre N.
TitleThe structure of HasB reveals a new class of TonB protein fold.
SourcePLoS One. 8:E58964-E58964(2013).
PubMed ID23527057

3AuthorsKoedding J. Killig F. Polzer P. Howard S.P. Diederichs K. Welte W.
TitleCrystal structure of a 92-residue C-terminal fragment of TonB from Escherichia coli reveals significant conformational changes compared to structures of smaller TonB fragments.
SourceJ. Biol. Chem. 280:3022-3028(2005).
PubMed ID15522863

5AuthorsKrieg S. Huche F. Diederichs K. Izadi-Pruneyre N. Lecroisey A. Wandersman C. Delepelaire P. Welte W.
TitleHeme uptake across the outer membrane as revealed by crystal structures of the receptor-hemophore complex.
SourceProc. Natl. Acad. Sci. U. S. A. 106:1045-1050(2009).
PubMed ID19144921

6AuthorsCobessi D. Meksem A. Brillet K.
TitleStructure of the heme/hemoglobin outer membrane receptor ShuA from Shigella dysenteriae: heme binding by an induced fit mechanism.
SourceProteins 78:286-294(2010).
PubMed ID19731368

7AuthorsOeemig J.S. Ollila O.H.S. Iwai H.
TitleNMR structure of the C-terminal domain of TonB protein from Pseudomonas aeruginosa.
SourcePeerJ 6:E5412-E5412(2018).
PubMed ID30186676

8AuthorsLundrigan M.D. Kadner R.J.
TitleNucleotide sequence of the gene for the ferrienterochelin receptor FepA in Escherichia coli. Homology among outer membrane receptors that interact with TonB.
SourceJ. Biol. Chem. 261:10797-10801(1986).
PubMed ID3015941

9AuthorsSchramm E. Mende J. Braun V. Kamp R.M.
TitleNucleotide sequence of the colicin B activity gene cba: consensus pentapeptide among TonB-dependent colicins and receptors.
SourceJ. Bacteriol. 169:3350-3357(1987).
PubMed ID2439491

11AuthorsNau C.D. Konisky J.
TitleEvolutionary relationship between the TonB-dependent outer membrane transport proteins: nucleotide and amino acid sequences of the Escherichia coli colicin I receptor gene.
SourceJ. Bacteriol. 171:1041-1047(1989).
PubMed ID2644220

4AuthorsGudmundsdottir A. Bell P.E. Lundrigan M.D. Bradbeer C. Kadner R.J.
TitlePoint mutations in a conserved region (TonB box) of Escherichia coli outer membrane protein BtuB affect vitamin B12 transport.
SourceJ. Bacteriol. 171:6526-6533(1989).
PubMed ID2687240

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