Abstract
In aerobic environments, iron exists as an insoluble ferric-oxihydroxide polymer with a concentration of soluble iron in a 10−16–10−18 M range. In the human body iron remains complexed with iron binding proteins. Both of these conditions create iron restricted environments for the growth of microorganisms. Iron is an essential element for the growth of a majority of microorganisms since iron acts as a cofactor for several important enzymes, and cytochromes involved in energy generation. Microorganisms employ many different strategies to acquire iron, among them siderophore-mediated iron transport, as the most common one. These types of transport systems are mostly found in Gram-negative bacteria, where they consist of outer membrane proteins, periplasmic binding proteins, inner membrane transport proteins, and energy transducing inner membrane protein complex TonB-ExbB-ExbD. The crystal structures of the outer membrane receptors FepA and FhuA from Escherichia coli were solved in late 1990s, but to date the mechanism of transport and energy transduction is not completely known. Enormous amounts of structural and biochemical data have been published in the past decade. This chapter pays tribute to the contributions of Dr. Dick van der Helm of the University of Oklahoma to the field of siderophore biology and discusses the structural advancement of the components involved in the siderophore mediated transport systems in E. coli.
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References
Abergel RJ, Clifton MC, Pizarro JC et al (2008) The siderocalin/enterobactin interaction: a link between mammalian immunity and bacterial iron transport. J Am Chem Soc 130:11524–11534
Abergel RJ, Moore EG, Strong RK et al (2006) Microbial evasion of the immune system: structural modifications of enterobactin impair siderocalin recognition. J Am Chem Soc 128:10998–10999
Bagg A, Neilands JB (1987) Molecular mechanism of siderophore-mediated iron assimilation. Microbiol Rev 51:509–518
Barnard TJ, Watson ME Jr, McIntosh MA (2001) Mutations in E. coli receptor FepA reveal residues involved in ligand binding and transport. Mol Microbiol 41:527–536
Barnes CL, Eng-Wilmot DL, van der Helm D (1984) Ferricrocin (C29H44FeN9O13.7H2O), an iron(III)-binding peptide from Aspergillus versicolor. Acta Cryst C40:922–926
Barnes CL, Hossain MB, Jalal MAF et al (1985) Ferrichrome conformations: ferrirubin, two crystal forms: C41H64FeN9O17.10.5H2O (I) and C41H64FeN9O17.CH3CN.H2O (II). Acta Cryst C41:341–347
Borths EL, Locher KP, Lee AT et al (2002) The structure of E. coli BtuF and binding to its cognate ATP binding cassette transporter. Proc Natl Acad Sci USA 99:16642–16647
Bradbeer C (1993) The proton motive force drives the outer membrane transport of cobalamin in Escherichia coli. J Bacteriol 175:3146–3150
Braun V (1995) Energy-coupled transport and signal transduction through the Gram-negative outer membrane via TonB-ExbB-ExbD-dependent receptor proteins. FEMS Microbiol Rev 16:295–307
Braun V (1997) Surface signaling: novel transcription initiation mechanism starting from the cell surface. Arch Microbiol 167:325–331
Braun V, Braun M (2002a) Active transport of iron and siderophore antibiotics. Curr Opinion Microbiol 5:194–200
Braun V, Braun M (2002b) Iron transport and signaling in E. coli. FEBS Lett 529:78–85
Braun V, Gaisser S, Herrmann C et al (1996) Energy-coupled transport across the outer membrane of E. coli: ExbB binds ExbD and TonB in vitro, and leucine 132 the periplasmic region and aspartate 25 in the transmembrane region are important for ExbD activity. J Bacteriol 178:2836–2845
Braun V, Hantke K, Koster W (1998) Bacterial iron transport: mechanism, genetics and regulation. In: Sigel A, Sigel H (eds) Metal ions in biological systems. Marcel Dekker, Inc., New York, pp 67–145
Braun V, Mahren S, Ogierman M (2003) Regulation of FecI-type ECF sigma factor by transmembrane signaling. Curr Opin Microbiol 6:173–180
Buchanan SK, Smith BS, Venkatramani L et al (1999) Crystal structure of the outer membrane active transporter FepA from Escherichia coli. Nature (Struct Biol) 6:56–63
Carter DM, Miousse IR, Gagnon JN et al (2006) Interactions between TonB from E. coli and the periplasmic protein FhuD. J Biol Chem 281:35413–35424
Chakraborty R, Lemke EA, Cao Z et al (2003) Identification and mutational studies of conserved amino acids in the outer membrane receptor protein, FepA, which affect transport but not binding of ferric-enterobactin in E. coli. Biometals 16:507–518
Chakraborty R, Storey E, van der Helm D (2007) Molecular mechanism of ferricsiderophore passage through the outer membrane receptor proteins of E. coli. Biometals 20:263–274
Chang C, Mooser A, Pluckthun A et al (2001) Crystal structure of the dimeric C-terminal domain of TonB reveals a novel fold. J Biol Chem 276:27535–27540
Chao TC, Becker A, Buhrmester J et al (2004) The Sinorhizobium meliloti fur gene regulates, with dependence on Mn(II), transcription of the sitABCD operon, encoding a metal-type transporter. J Bacteriol 186:3609–3620
Chimento DP, Kadner RJ, Wiener MC (2005) Comparative structural analysis of TonB-dependent outer membrane transporters: implications for the transport cycle. Protein Struct Funct Bioinformatics 59:240–251
Chimento DP, Mohanti AK, Kadner RJ et al (2003) Substrate-induced transmembrane signaling in the cobalamin transporter BtuB. Nat Struct Biol 10:394–401
Chu BC, Garcia-Herrero A, Johanson TH et al (2010) Siderophore uptake in bacteria and the battle for iron with the host; a birds’s eye view. Biometals 23:597–599
Clarke TE, Braun V, Winkelmann G et al (2002) X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin. J Biol Chem 277:13966–13972
Clarke TE, Ku S, Dougan DR et al (2000) The structure of the ferric siderophore binding protein FhuD complexed with gallichrome. Nat Struct Biol 7:287–291
Cobessi D, Celia H, Pattus F (2005a) Structure of ferric-pyochelin and its membrane receptor FptA from P. aeruginosa. J Mol Biol 352:893–904
Cobessi D, Herve C, Folschweiller N et al (2005b) The Crystal structure of the pyoverdine outer membrane receptor FpvA from P. aeruginosa at 3.6 Å resolution. J Mol Biol 347:121–134
Crosa JH (1989) Genetics and molecular biology of siderophore-mediated iron transport in bacteria. Microbiol Rev 53:517–530
Crosa JH (1997) Signal transduction and transcriptional and postranscriptional control of iron-regulated genes in bacteria. Microbiol Mol Biol Rev 61:319–336
de Lorenzo V, Herrero M, Giovannini F et al (1988) Fur (ferric uptake regulation) protein and CAP (catabolite-activtor protein) modulate transcription of fur gene in Escherichia coli. Eur J Biochem 173:537–546
Eisenhauer HA, Shames S, Pawelek PD et al (2005) Siderophore transport through E. coli outer membrane receptor FhuA with disulfide-tethered cork and barrel domains. J Biol Chem 280:30574–30580
Ferguson A, Chakraborty R, Barbara S et al (2002) Structural basis of gating by the outer membrane transporter FecA. Science 295:1715–1719
Ferguson AD, Deisenhofer J (2004) Metal import through microbial membranes. Cell 116:15–24
Ferguson AD, Hofmann E, Coulton JW et al (1998) Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide. Science 282:2215–2220
Ferguson AD, Amezcua CA, Halabi NM et al (2006) Signal transduction pathway of TonB-dependent transporters. Proc Natl Acad Sci USA 104:513–518
Francis JJ, Macturk HM, Madinaveitia J et al (1949) Isolation from acid-fast bacteria of a growth-factor for Mycobacterium johnei and of a precursor of phthiocol. Nature 163:365–366
Frost GE, Rosenberg H (1973) The inducible citrate-dependent iron transport system in Escherichia coli K12. Biochem Biophys Acta 330:90–101
Garcia-Herrero A, Peacock RS, Howard SP et al (2007) The solution structure of the periplasmic domain of the TonB system ExbD protein reveals an unexpected structural homology with siderophore-binding proteins. Mol Microbiol 66:872–889
Garcia-Herrero A, Vogel HJ (2005) Nuclear magnetic resonance solution structure of the periplasmic signaling domain of the TonB-dependent outer membrane transporter FecA from E. coli. Mol Microbiol 58:1226–1237
Germon P, Ray MC, Vianney A et al (2001) Energy-dependent conformational change in the TolA protein of E. coli involves its N-terminal domain, TolQ and TolR. J Bacteriol 183:4110–4114
Ghosh J, Postle K (2005) Disulphide trapping of an in vivo energy-dependent conformation of Escherichia coli TonB protein. Mol Microbiol 55:276–288
Gresock MG, Savenkova MI, Larsen RA et al (2011) Death of the TonB shuttle hypothesis. . doi:10.3389/fmicb.2011.00206
Gudmundsdottir A, Bell PE, Lundrigan MD et al (1989) Point mutations in a conserved region (TonB box) of Escherichia coli outer membrane protein BtuB affect vitamin B12 transport. J Bacteriol 171:6526–6533
Gumbart J, Weiner MC, Tajkhorshid E (2007) Mechanics of force propagation in TonB dependent outer membrane transport. Biophysical J 93:496–504
Hantke K (1984) Cloning of the repressor protein gene of iron-regulated systems in Escherichia coli K12. Mol Gen Genet 197:337–341
Higgs PI, Larsen RA, Postle K (2002) Quantification of known components of the Escherichia coli TonB energy transduction system: TonB, ExbB, ExbD and FepA. Mol Microbiol 44:271–281
Hough E, Rogers D (1974) Crystal structure of ferrimycobactin P, a growth factor for the mycobacteria. Biochem Biophys Res Commun 57:73–77
Jalal MA, Mocharla R, Barnes CL et al (1984a) Extracellular siderophores from Aspergillus ochraceous. J Bacteriol 158:683–688
Jalal MA, Mocharla R, van der Helm D (1984b) Separation of ferrichromes and other hydroxamate siderophores of fungal origin by reversed-phase chromatography. J Chromat 301:247–252
Jalal MAF, van der Helm D (1989) Purification and crystallization of ferric enterobactin receptor protein, FepA, from the outer membranes of E. coli UT5600/pbb2. FEBS Lett 243:366–370
Jana B, Manning M, Postle K (2011) Mutations in the ExbB cytoplasmic carboxy terminus prevent energy-dependent interaction between the TonB and ExbD periplasmic domains. J Bacteriol 193:5649–5657
Killmann H, Videnov G, Jung G et al (1995) Identification of receptor binding sites by competitive peptide Mapping: phages T1, T5, and 80 and colicin M bind to the gating loop of FhuA. J Bacteriol 177:694–698
Ködding J, Killig F, Howard SP et al (2004) Dimerization of TonB is not essential for its binding to the outer membrane siderophore receptor FhuA of E. coli. J Biol Chem 279:9978–9986
Ködding J, Killig F, Polzer P et al (2005) Crystal structure of a 92-residue C-terminal fragment of TonB from E. coli reveals significant conformational changes compared to structures of smaller TonB fragments. J Biol Chem 280:3022–3088
Krewulak KD, Vogel HJ (2008) Structural biology of bacterial iron uptake. Bioch Biophys Acta 1778:1781–1804
Larson RA, Letain TE, Postle K (1999) Protonmotive force, ExbB and ligand-bound FepA drive conformational changes in TonB. Mol Microbiol 31:1809–1824
Lo Conte L, Chothia C, Janin J (1999) The atomic structure of protein–protein recognition sites. J Mol Biol 285:2177–2198
Locher KP, Borths E (2004) ABC transporter architecture and mechanism: implications from the crystal structures of BtuCD and BtuF. FEBS Lett 564:264–268
Locher KP, Rees B, Koebnik R et al (1998) Transmembrane signaling across the ligand-gated FhuA receptor: crystal structures of free and ferrichrome-bound states reveal allosteric changes. Cell 95:771–778
Lundrigan MD, Kadner RJ (1986) Nucleotide sequence of the gene for the ferrienterochelin receptor FepA in E. coli. J Biol Chem 261:10797–10801
Neilands JB (1981) Microbial iron compounds. Ann Rev Biochem 50:715–731
Neilands JB (1952) A crystalline organo-iron pigment from the smut fungus Ustilago sphaerogena. J Am Chem Soc 74:4846–4847
Newton SMC, Igo JD, Scott DC et al (1999) Effect of loop deletion on the binding and transport of ferric enterobactin by FepA. Mol Microbiol 32:1153–1165
Noinaj N, Guillier M, Barnard TJ et al (2010) TonB dependent transporters: regulation, structure, and function. Annu Rev Microbiol 64:43–60
Ollis AA, Kumar A, Postle K (2012) The ExbD periplasmic domain contains distinct functional regions for two stages in TonB energization. J Bacteriol 194:3069–3077
Ollis AA, Postle K (2011) The same periplasmic ExbD residues mediate in vivo interactions between ExbD homodimers and ExbD-TonB heterodimers. J Bacteriol 193:6852–6863
Ollis AA, Postle K (2012a) Identification of functionally important TonB-ExbD periplasmic domain interactions in vivo. J Bacteriol 194:3078–3087
Ollis AA, Postle K (2012b) ExbD mutants define initial stages in TonB energization. J Mol Biol 415:237–247
Pawelek PD, Croteau N, Ng-Thow-Hing C et al (2006) Structure of TonB in complex with FhuA, E. coli outer membrane receptor. Science 312:1399–1402
Peacock RS, Weljie AM, Howard SP et al (2005) The solution structure of the C-terminal domain of TonB and interactions studies with TonB box peptides. J Mol Biol 345:1185–1197
Pohl E, Haller J, Mijovilovich A et al (2003) Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator. Mol Microbiol 47:903–915
Postle K (1993) TonB protein and energy transduction between membranes. J Bioenerg Biomembr 25:591–601
Postle K, Kastead K A, Gresock MG et al. (2010) The TonB dimeric crystal structures do not exist in vivo. mBio 1:e00307–003010. doi:10.1128/mBio.00307-10
Pramanik A, Hauf W, Hoffmann J et al (2011) Oligomeric structure of ExbB and ExbB-ExbD isolated from E. coli as revealed by LILBID mass spectrometry. Biochemistry 50:8950–8956
Pramanik A, Zhang F, Schwarz H, Schreiber F et al (2010) ExbB protein in the cytoplasmic membrane of E. coli forms a stable oligomer. Biochemistry 49:8721–8728
Raymond K, Dertz RE, Kim SS (2003) Enterobactin: an archetype for microbial iron transport. Proc Natl Acad Sci 100:3584–3588
Rousseau F, Schymkowitz JW, Itzhaki LS (2003) The unfolding story of three-dimensional domain swapping. Structure (Camb.) 11:243–251
Sauer M, Hantke K, Braun V (1990) Sequence of the fhuE outer-membrane receptor gene of Escherichia coli K12 and properties of mutants. Mol Microbiol 4:427–437
Sauter A, Howard SP, Braun V (2003) In vivo evidence for TonB dimerization. J Bacteriol 185:5747–5754
Schauer K, Gouget B, Carriere M et al (2007) Novel nickel transport mechanism across the bacterial outer membrane energized by the TonB/ExbB/ExbD machinery. Mol Microbiol 63:1054–1068
Sen TZ, Kloster M, Jemigan RL et al (2008) Predicting the complex structure and functional motions of the outer membrane transporter and signal transducer FecA. Biophysical J 94:2482–2491
Sheikh A, Taylor GL (2009) Crystal structure of the Vibrio cholerae ferric uptake regulator (Fur) reveals insights into metal co-ordination. Mol Microbiol 72:1208–1220
Shultis DD, Purdy MD, Banchs CN et al (2006) Outer membrane active transport: Structure of the BtuB: TonB complex. Science 312:1396–1399
Skare JT, Ahmer BMM, Seachord CL et al (1993) Energy transduction between membranes. J Biol Chem 268:16302–16308
Teintze M, Hossain MB, Barnes CL et al (1981) Structure of ferric pseudobactin, a siderophore from a plant growth promoting Pseudomonas. Biochemistry 20:6446–6457
Todd JD, Wexler M, Sawers G et al (2002) RirA, an iron-responsive regulator in the symbiotic bacterium Rhizobium leguminosarum. Microbiology 148:4059–4071
Tsai CJ, Lin SL, Wolfson HJ et al (1997) Studies of protein–protein interfaces: a statistical analysis of the hydrophobic effect. Protein Sci 6:53–64
Twort FW, Ingram GLY (1912) A method for isolating and cultivating Mycobacterium enteritidis chronicae pseudotuberculosis bovis, Johne, and some experiments on the preparation of a diagnostic vaccine for pseudotuberculosis enteritis of bovines. Proc R Soc Lond Ser B 84:517–542
Vakharia-Rao H, Kastead KA, Savenkova MI et al (2007) Deletion and substitution analysis of E. coli TonB Q160 region. J Bacteriol 189:4662–4670
van der Helm D (2004) Structure of outer membrane receptor proteins pp 51–65. In: Crosa JH, Mey AR, Payne SM (eds) Iron transport in bacteria. ASM press, Washington
van der Helm D, Baker JR, Eng-Wilmot DL et al (1980) Crystal structure of ferrichrome and a comparison with the structure of ferrichrome A. J Am Chem Soc 102:4224–4231
van der Helm D, Baker JR, Loghry RA et al (1981) Structures of alumichrome A and ferrichrome A at low temperature. Acta Cryst B37:323–330
van der Helm D, Chakraborty R (2002) Structures of siderophore receptors. In: Winkelmann G (ed) Microbial transport systems. Wiley, Weinheim, pp 261–288
van der Helm D, Chakraborty R, Ferguson AD et al (2002) Bipartite gating in the outer membrane protein FecA. Biochem Soc Trans 30:708–710
van der Helm D, Poling M (1976) The crystal structure of ferrioxamine E. J Am Chem Soc 98:82–86
Wexler M, Todd JD, Kolade O et al (2003) Fur is not the global regulator of iron uptake genes in Rhizobium leguminosarum. Microbiology 149:1357–1365
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Chakraborty, R. (2013). Ferric Siderophore Transport via Outer Membrane Receptors of Escherichia coli: Structural Advancement and A Tribute to Dr. Dick van der Helm—an ‘Ironman’ of Siderophore Biology. In: Chakraborty, R., Braun, V., Hantke, K., Cornelis, P. (eds) Iron Uptake in Bacteria with Emphasis on E. coli and Pseudomonas. SpringerBriefs in Molecular Science(). Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6088-2_1
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