Disease relevance of tonB

• Vibrio cholerae has multiple iron acquisition systems, including TonB-dependent transport of heme and of the catechol siderophore vibriobactin [1].
• Molecular characterization of eutF mutants of Salmonella typhimurium LT2 identifies eutF lesions as partial-loss-of-function tonB alleles [2].
• FhuA, the receptor for ferrichrome-iron in Escherichia coli, is a member of a family of integral outer membrane proteins, which, together with the energy-transducing protein TonB, mediate the active transport of ferric siderophores across the outer membrane of Gram-negative bacteria [3].
• In Gram-negative bacteria, TonB-dependent outer membrane proteins form energized, gated pores that bind iron chelates (siderophores) and internalize them [4].
• Hemin uptake system of Yersinia enterocolitica: similarities with other TonB-dependent systems in gram-negative bacteria [5].

High impact information on tonB

• Sequence homologies and mutagenesis data are used to propose a structural mechanism for TonB-dependent siderophore-mediated transport across the outer membrane [3].
• The sequence homology among TonB-dependent proteins suggests that all ligand-specific outer membrane receptors may function by this gated-porin mechanism [6].
• Point mutants in FecA displayed the constitutive expression of fec transport genes in the absence of ferric citrate but still required TonB, with the exception of one FecA mutant which showed a TonB-independent induction [7].
• A characteristic feature of TonB-dependent transporters is the Ton box, a conserved sequence near the N terminus and exposed to the periplasm [8].
• In TonB-dependent transporters, a conserved sequence of seven residues, the Ton box, faces the periplasm and interacts with the inner membrane TonB protein to energize an active transport cycle [9].

Chemical compound and disease context of tonB

• The predicted NH2 terminus of tonB protein resembles the proteolytically cleaved signal sequences of E. coli periplasmic and outer membrane proteins; the overall hydrophilic character of the protein sequence suggests that the bulk of the tonB protein is not embedded within the inner or outer membrane [10].
• Nucleotide sequence of the gene for the ferrienterochelin receptor FepA in Escherichia coli. Homology among outer membrane receptors that interact with TonB [11].
• The conserved proline-rich motif is not essential for energy transduction by Escherichia coli TonB protein [12].
• In contrast to the TonB proteins of E. coli and Salmonella typhimurium, translation of the S. marcescens TonB protein starts at the first methionine residue of the open reading frame, which is the only amino acid removed during TonB maturation and export [13].
• Tandem duplication of the E. coli (EP)X(KP) region by insertion of the S. marcescens (EP)X(KP) region (38 residues) and replacement of lysine residue 91 by glutamate did not alter TonB activity so that no evidence was obtained for this region to be implicated in receptor binding [14].

Biological context of tonB

• The molecular characterization of the mutation that corrected the Eut- phenotype caused by allele Delta903 showed that the new mutation was a deletion of two nucleotides at the tonB-trpA fusion site [2].
• The receptor-binding domain of TonB appears to be formed by a highly conserved C-terminal amino acid sequence of approximately 100 residues [15].
• To accomplish energy transfer, TonB contacts outer membrane receptors [16].
• TonB-dependent transducers might be important for pathogenicity; therefore, a survey of their presence in bacteria was aimed [17].
• Point mutations were introduced into the TonB-box region of the colicin B structural gene cba resulting in colicin B derivatives which were partially or totally inactive against E. coli cells [18].

Anatomical context of tonB

• Energy flows from the cytoplasmic into the outer membrane via a complex consisting of the TonB, ExbB and ExbD proteins which are anchored in the cytoplasmic membrane [19].
• Energy transduction between membranes. TonB, a cytoplasmic membrane protein, can be chemically cross-linked in vivo to the outer membrane receptor FepA [20].
• To determine the importance of the individual TonB-dependent iron transport systems during urinary tract infections, mutants defective in each of the CFT073 high-affinity iron transport systems were constructed and tested in the mouse model [21].
• These results indicate that TonB-mediated iron uptake contributes to colonization of the Peyer's patches and mesenteric lymph nodes but not the liver and spleen of the mouse [22].
• The TonB protein located in the cell wall of Gram-negative bacteria mediates the proton motive force from the cytoplasmic membrane to specific outer membrane transporters [23].

Associations of tonB with chemical compounds

• Interaction between TonB and two of the TonB-dependent siderophore transporters has been detected previously by formaldehyde crosslinking [24].
• A significant discrepancy exists between the calculated size of tonB protein and the apparent size of 36 kilodaltons determined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis [10].
• TonB also possesses two distinct binding regions: one in the C terminus of the protein, for which binding to FhuA is ferricrocin-independent, and a higher affinity region outside the C terminus, for which ferricrocin enhances interactions with FhuA [16].
• FhuD residue Thr-181, located within the siderophorebinding site and mapping to a predicted TonB-interaction surface, was mutated to cysteine [25].
• In this report, we show, by Edman degradation of [35S]methionine-labeled protein, that TonB protein synthesized in vitro initiates at the third of these methionine codons [26].

Analytical, diagnostic and therapeutic context of tonB

• In this study, analyses of FhuA interactions with two recombinant TonB proteins by analytical ultracentrifugation revealed that TonB forms a 2:1 complex with FhuA [16].
• The PCR mutagenesis strategy targeted the N-terminus because it forms a plug inside the FepA barrel that is expected to be involved in ligand binding, ligand transport, and interaction with TonB [27].
• Purified FhuA peptides fused to MBP bound specifically to TonB by ELISA [28].
• Further, site-directed mutagenesis of the TonB box -1 residue in a V. cholerae TonB2-dependent receptor demonstrated that a large hydrophobic amino acid in this position promotes recognition of V. cholerae TonB1 [29].
• On the basis of the multiple progressive sequence alignment and the similarity scores derived from it, a tree representing evolutionary distance between five TonB-dependent outer membrane transport proteins was generated [30].

References