Cellular and Molecular Life Sciences

, Volume 67, Issue 3, pp 341–351 | Cite as

Dps-like proteins: structural and functional insights into a versatile protein family

Review

Abstract

Dps-like proteins are key factors involved in the protection of prokaryotic cells from oxidative damage. They act by either oxidizing iron to prevent the formation of oxidative radicals or by forming Dps-DNA complexes to physically protect DNA. All Dps-like proteins are characterized by a common three-dimensional architecture and are found as spherical dodecamers with a hollow central cavity. Despite their structural similarities, recent biochemical and structural data have suggested different functions among members of the family that range from protection inside the cells in response to various stress signals to adhesion and virulence during bacterial infections. Moreover, the Dps-like proteins have lately attracted considerable interest in the field of nanotechnology owing to their ability to act as protein cages for iron and various other metals. A better understanding of their function and mechanism could therefore lead to novel applications in biotechnology and nanotechnology.

Keywords

Oxidative stress Mini-ferritins Metal binding Ferroxidase Fenton reaction Iron binding Zinc 

Supplementary material

18_2009_168_MOESM1_ESM.doc (38 kb)
Supplementary, Table SI (DOC 10 kb)
18_2009_168_MOESM2_ESM.tif (14.8 mb)
Figure S1. Sequence alignment of Dps-family representatives. The secondary structures are presented according to E. coli Dps. The blue triangles indicate the iron-binding residues at the mono-iron ferroxidase center. The blue boxes show residues that share at least 70% similarity in physico-chemical properties. Figure was created with ESPript (http://www.espript.ibcp.fr/). (TIF 3391 kb)

References

  1. 1.
    Williams RJ (1982) Free manganese (II) and iron (II) cations can act as intracellular cell controls. FEBS Lett 140:3–10CrossRefPubMedGoogle Scholar
  2. 2.
    Storz G, Imlay JA (1999) Oxidative stress. Curr Opin Microbiol 2:188–194CrossRefPubMedGoogle Scholar
  3. 3.
    Imlay JA (2008) Cellular defences against superoxide and hydrogen peroxide. Annu Rev Biochem 77:755–776CrossRefPubMedGoogle Scholar
  4. 4.
    Almirón M, Link AJ, Furlong D, Kolter R (1992) A novel DNA-binding protein with regulatory and protective roles in starved Escherichia coli. Genes Dev 6:2646–2654CrossRefPubMedGoogle Scholar
  5. 5.
    Bozzi M, Mignogna G, Stefanini S, Barra D, Longhi C, Valenti P, Chiancone E (1997) A novel non-heme iron-binding ferritin related to the DNA-binding proteins of the Dps family in Listeria innocua. J Biol Chem 272:3259–3265CrossRefPubMedGoogle Scholar
  6. 6.
    Chen L, Helmann JD (1995) Bacillus subtilis MrgA is a Dps(PexB) homologue: evidence for metalloregulation of an oxidative-stress gene. Mol Microbiol 18:295–300CrossRefPubMedGoogle Scholar
  7. 7.
    Gupta S, Chatterji D (2003) Bimodal protection of DNA by Mycobacterium smegmatis DNA-binding protein from stationary phase cells. J Biol Chem 278:5235–5241CrossRefPubMedGoogle Scholar
  8. 8.
    Halsey TA, Vazquez-Torres A, Gravdahl DJ, Fang FC, Libby SJ (2004) The ferritin-like Dps protein is required for Salmonella enterica serovar Typhimurium oxidative stress resistance and virulence. Infect Immun 72:1155–1158CrossRefPubMedGoogle Scholar
  9. 9.
    Papinutto E, Dundon WG, Pitulis N, Battistutta R, Montecucco C, Zanotti G (2002) Structure of two iron-binding proteins from Bacillus anthracis. J Biol Chem 277:15093–15098CrossRefPubMedGoogle Scholar
  10. 10.
    Ramsay B, Wiedenheft B, Allen M, Gauss GH, Lawrence CM, Young M, Douglas T (2006) Dps-like protein from the hyperthermophilic archaeon Pyrococcus furiosus. J Inorg Biochem 100:1061–1068CrossRefPubMedGoogle Scholar
  11. 11.
    Yamamoto Y, Poole LB, Hantgan RR, Kamio Y (2002) An iron-binding protein, Dpr, from Streptococcus mutans prevents iron-dependent hydroxyl radical formation in vitro. J Bacteriol 184:2931–2939CrossRefPubMedGoogle Scholar
  12. 12.
    Grant RA, Filman DJ, Finkel SE, Kolter R, Hogle JM (1998) The crystal structure of Dps, a ferritin homolog that binds and protects DNA. Nat Struct Biol 5:294–303CrossRefPubMedGoogle Scholar
  13. 13.
    Ilari A, Stefanini S, Chiancone E, Tsernoglou D (2000) The dodecameric ferritin from Listeria innocua contains a novel intersubunit iron-binding site. Nat Struct Biol 7:38–43CrossRefPubMedGoogle Scholar
  14. 14.
    Ren B, Tibbelin G, Kajino T, Asami O, Ladenstein R (2003) The multi-layered structure of Dps with a novel di-nuclear ferroxidase center. J Mol Biol 329:467–477CrossRefPubMedGoogle Scholar
  15. 15.
    Romao CV, Mitchell EP, McSweeney S (2006) The crystal structure of Deinococcus radiodurans Dps protein (DR2263) reveals the presence of a novel metal centre in the N terminus. J Biol Inorg Chem 11:891–902CrossRefPubMedGoogle Scholar
  16. 16.
    Kauko A, Haataja S, Pulliainen AT, Finne J, Papageorgiou AC (2004) Crystal structure of Streptococcus suis Dps-like peroxide resistance protein Dpr: implications for iron incorporation. J Mol Biol 338:547–558CrossRefPubMedGoogle Scholar
  17. 17.
    Franceschini S, Ceci P, Alaleona F, Chiancone E, Ilari A (2006) Antioxidant Dps protein from the thermophilic cyanobacterium Thermosynechococcus elongatus. FEBS J 273:4913–4928CrossRefPubMedGoogle Scholar
  18. 18.
    Zanotti G, Papinutto E, Dundon W, Battistutta R, Seveso M, Giudice G, Rappuoli R, Montecucco C (2002) Structure of the neutrophil-activating protein from Helicobacter pylori. J Mol Biol 323:125–130CrossRefPubMedGoogle Scholar
  19. 19.
    Zeth K, Offermann S, Essen LO, Oesterhelt D (2004) Iron-oxo clusters biomineralizing on protein surfaces: structural analysis of Halobacterium salinarum DpsA in its low- and high-iron states. Proc Natl Acad Sci USA 101:13780–13785CrossRefPubMedGoogle Scholar
  20. 20.
    Gauss GH, Benas P, Wiedenheft B, Young M, Douglas T, Lawrence CM (2006) Structure of the DPS-like protein from Sulfolobus solfataricus reveals a bacterioferritin-like dimetal binding site within a DPS-like dodecameric assembly. Biochemistry 45:10815–10827CrossRefPubMedGoogle Scholar
  21. 21.
    Thumiger A, Polenghi A, Papinutto E, Battistutta R, Montecucco C, Zanotti G (2006) Crystal structure of antigen TpF1 from Treponema pallidum. Proteins 62:827–830CrossRefPubMedGoogle Scholar
  22. 22.
    Perrin C, Guimont C, Bracquart P, Gaillard JL (1999) Expression of a new cold shock protein of 21.5 kDa and of the major cold shock protein by Streptococcus thermophilus after cold shock. Curr Microbiol 39:342–347CrossRefPubMedGoogle Scholar
  23. 23.
    Hébraud M, Guzzo J (2000) The main cold shock protein of Listeria monocytogenes belongs to the family of ferritin-like proteins. FEMS Microbiol Lett 190:29–34CrossRefPubMedGoogle Scholar
  24. 24.
    Nicodeme M, Perrin C, Hols P, Bracquart P, Gaillard JL (2004) Identification of an iron-binding protein of the Dps family expressed by Streptococcus thermophilus. Curr Microbiol 48:51–56CrossRefPubMedGoogle Scholar
  25. 25.
    Ali Azam T, Iwata A, Nishimura A, Ueda S, Ishihama A (1999) Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid. J Bacteriol 181:6361–6370PubMedGoogle Scholar
  26. 26.
    Rocha ER, Owens GJ, Smith CJ (2000) The redox-sensitive transcriptional activator OxyR regulates the peroxide response regulon in the obligate anaerobe Bacteroides fragilis. J Bacteriol 182:5059–5069CrossRefPubMedGoogle Scholar
  27. 27.
    Ueshima J, Shoji M, Ratnayake DB, Abe K, Yoshida S, Yamamoto K, Nakayama K (2003) Purification, gene cloning, gene expression, and mutants of Dps from the obligate anaerobe Porphyromonas gingivalis. Infect Immun 71:1170–1178CrossRefPubMedGoogle Scholar
  28. 28.
    Stephani K, Weichart D, Hengge R (2003) Dynamic control of Dps protein levels by ClpXP and ClpAP proteases in Escherichia coli. Mol Microbiol 49:1605–1614CrossRefPubMedGoogle Scholar
  29. 29.
    Chodavarapu S, Gomez R, Vicente M, Kaguni JM (2008) Escherichia coli Dps interacts with DnaA protein to impede initiation: a model of adaptive mutation. Mol Microbiol 67:1331–1346CrossRefPubMedGoogle Scholar
  30. 30.
    Bsat N, Herbig A, Casillas-Martinez L, Setlow P, Helmann JD (1998) Bacillus subtilis contains multiple Fur homologues: identification of the iron uptake (Fur) and peroxide regulon (PerR) repressors. Mol Microbiol 29:189–198CrossRefPubMedGoogle Scholar
  31. 31.
    Horsburgh MJ, Clements MO, Crossley H, Ingham E, Foster SJ (2001) PerR controls oxidative stress resistance and iron storage proteins and is required for virulence in Staphylococcus aureus. Infect Immun 69:3744–3754CrossRefPubMedGoogle Scholar
  32. 32.
    Brenot A, King KY, Caparon MG (2005) The PerR regulon in peroxide resistance and virulence of Streptococcus pyogenes. Mol Microbiol 55:221–234CrossRefPubMedGoogle Scholar
  33. 33.
    Ishikawa T, Mizunoe Y, Kawabata S, Takade A, Harada M, Wai SN, Yoshida S (2003) The iron-binding protein Dps confers hydrogen peroxide stress resistance to Campylobacter jejuni. J Bacteriol 185:1010–1017CrossRefPubMedGoogle Scholar
  34. 34.
    Olsen KN, Larsen MH, Gahan CG, Kallipolitis B, Wolf XA, Rea R, Hill C, Ingmer H (2005) The Dps-like protein Fri of Listeria monocytogenes promotes stress tolerance and intracellular multiplication in macrophage-like cells. Microbiology 151:925–933CrossRefPubMedGoogle Scholar
  35. 35.
    Li X, Pal U, Ramamoorthi N, Liu X, Desrosiers DC, Eggers CH, Anderson JF, Radolf JD, Fikrig E (2007) The Lyme disease agent Borrelia burgdorferi requires BB0690, a Dps homologue, to persist within ticks. Mol Microbiol 63:694–710PubMedGoogle Scholar
  36. 36.
    Montemurro P, Barbuti G, Dundon WG, Del Giudice G, Rappuoli R, Colucci M, De Rinaldis P, Montecucco C, Semeraro N, Papini E (2001) Helicobacter pylori neutrophil-activating protein stimulates tissue factor and plasminogen activator inhibitor-2 production by human blood mononuclear cells. J Infect Dis 183:1055–1062CrossRefPubMedGoogle Scholar
  37. 37.
    D’Elios MM, Appelmelk BJ, Amedei A, Bergman MP, Del Prete G (2004) Gastric autoimmunity: the role of Helicobacter pylori and molecular mimicry. Trends Mol Med 10:316–323CrossRefPubMedGoogle Scholar
  38. 38.
    Evans DJ Jr, Evans DG, Takemura T, Nakano H, Lampert HC, Graham DY, Granger DN, Kvietys PR (1995) Characterization of a Helicobacter pylori neutrophil-activating protein. Infect Immun 63:2213–2220PubMedGoogle Scholar
  39. 39.
    Montemurro P, Nishioka H, Dundon WG, de Bernard M, Del Giudice G, Rappuoli R, Montecucco C (2002) The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a potent stimulant of mast cells. Eur J Immunol 32:671–676CrossRefPubMedGoogle Scholar
  40. 40.
    Brisslert M, Enarsson K, Lundin S, Karlsson A, Kusters JG, Svennerholm AM, Backert S, Quiding-Jarbrink M (2005) Helicobacter pylori induce neutrophil transendothelial migration: role of the bacterial HP-NAP. FEMS Microbiol Lett 249:95–103CrossRefPubMedGoogle Scholar
  41. 41.
    Polenghi A, Bossi F, Fischetti F, Durigutto P, Cabrelle A, Tamassia N, Cassatella MA, Montecucco C, Tedesco F, de Bernard M (2007) The neutrophil-activating protein of Helicobacter pylori crosses endothelia to promote neutrophil adhesion in vivo. J Immunol 178:1312–1320PubMedGoogle Scholar
  42. 42.
    Amedei A, Cappon A, Codolo G, Cabrelle A, Polenghi A, Benagiano M, Tasca E, Azzurri A, D’Elios MM, Del Prete G, de Bernard M (2006) The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses. J Clin Invest 116:1092–1101CrossRefPubMedGoogle Scholar
  43. 43.
    Peña MM, Bullerjahn GS (1995) The DpsA protein of Synechococcus sp. strain PCC7942 is a DNA-binding hemoprotein. Linkage of the Dps and bacterioferritin protein families. J Biol Chem 270:22478–22482CrossRefPubMedGoogle Scholar
  44. 44.
    Kottakis F, Befani C, Asiminas A, Kontou M, Koliakos G, Choli-Papadopoulou T (2009) The C-terminal region of HPNAP activates neutrophils and promotes their adhesion to endothelial cells. Helicobacter 14:177–179CrossRefPubMedGoogle Scholar
  45. 45.
    Stillman TJ, Upadhyay M, Norte VA, Sedelnikova SE, Carradus M, Tzokov S, Bullough PA, Shearman CA, Gasson MJ, Williams CH, Artymiuk PJ, Green J (2005) The crystal structures of Lactococcus lactis MG1363 Dps proteins reveal the presence of an N-terminal helix that is required for DNA binding. Mol Microbiol 57:1101–1112CrossRefPubMedGoogle Scholar
  46. 46.
    Roy S, Saraswathi R, Gupta S, Sekar K, Chatterji D, Vijayan M (2007) Role of N and C-terminal tails in DNA binding and assembly in Dps: structural studies of Mycobacterium smegmatis Dps deletion mutants. J Mol Biol 370:752–767CrossRefPubMedGoogle Scholar
  47. 47.
    Yang X, Chen-Barrett Y, Arosio P, Chasteen ND (1998) Reaction paths of iron oxidation and hydrolysis in horse spleen and recombinant human ferritins. Biochemistry 37:9743–9750CrossRefPubMedGoogle Scholar
  48. 48.
    Yang X, Chiancone E, Stefanini S, Ilari A, Chasteen ND (2000) Iron oxidation and hydrolysis reactions of a novel ferritin from Listeria innocua. Biochem J 349(3):783–786PubMedGoogle Scholar
  49. 49.
    Yang X, Le Brun NE, Thomson AJ, Moore GR, Chasteen ND (2000) The iron oxidation and hydrolysis chemistry of Escherichia coli bacterioferritin. Biochemistry 39:4915–4923CrossRefPubMedGoogle Scholar
  50. 50.
    Zhao G, Ceci P, Ilari A, Giangiacomo L, Laue TM, Chiancone E, Chasteen ND (2002) Iron and hydrogen peroxide detoxification properties of DNA-binding protein from starved cells. A ferritin-like DNA-binding protein of Escherichia coli. J Biol Chem 277:27689–27696CrossRefPubMedGoogle Scholar
  51. 51.
    Su M, Cavallo S, Stefanini S, Chiancone E, Chasteen ND (2005) The so-called Listeria innocua ferritin is a Dps protein. Iron incorporation, detoxification, and DNA protection properties. Biochemistry 44:5572–5578CrossRefPubMedGoogle Scholar
  52. 52.
    Bellapadrona G, Stefanini S, Zamparelli C, Theil EC, Chiancone E (2009) Iron translocation into and out of Listeria innocua Dps and size distribution of the protein-enclosed nanomineral are modulated by the electrostatic gradient at the 3-fold “ferritin-like” pores. J Biol Chem 284:19101–19109CrossRefPubMedGoogle Scholar
  53. 53.
    Kauko A, Pulliainen AT, Haataja S, Meyer-Klaucke W, Finne J, Papageorgiou AC (2006) Iron incorporation in Streptococcus suis Dps-like peroxide resistance protein Dpr requires mobility in the ferroxidase center and leads to the formation of a ferrihydrite-like core. J Mol Biol 364:97–109CrossRefPubMedGoogle Scholar
  54. 54.
    Ilari A, Ceci P, Ferrari D, Rossi GL, Chiancone E (2002) Iron incorporation into Escherichia coli Dps gives rise to a ferritin-like microcrystalline core. J Biol Chem 277:37619–37623CrossRefPubMedGoogle Scholar
  55. 55.
    Castruita M, Saito M, Schottel PC, Elmegreen LA, Myneni S, Stiefel EI, Morel FM (2006) Overexpression and characterization of an iron storage and DNA-binding Dps protein from Trichodesmium erythraeum. Appl Environ Microbiol 72:2918–2924CrossRefPubMedGoogle Scholar
  56. 56.
    Eggleton RA, Fitzpatrick RW (1988) New data and a revised structural model for ferrihydrite. Clays Clay Miner 36:111–124CrossRefGoogle Scholar
  57. 57.
    Castruita M, Elmegreen LA, Shaked Y, Stiefel EI, Morel FM (2007) Comparison of the kinetics of iron release from a marine (Trichodesmium erythraeum) Dps protein and mammalian ferritin in the presence and absence of ligands. J Inorg Biochem 101:1686–1691CrossRefPubMedGoogle Scholar
  58. 58.
    Johnson JL, Cannon M, Watt RK, Frankel RB, Watt GD (1999) Forming the phosphate layer in reconstituted horse spleen ferritin and the role of phosphate in promoting core surface redox reactions. Biochemistry 38:6706–6713CrossRefPubMedGoogle Scholar
  59. 59.
    Flenniken ML, Uchida M, Liepold LO, Kang S, Young MJ, Douglas T (2009) A library of protein cage architectures as nanomaterials. Curr Top Microbiol Immunol 327:71–93CrossRefPubMedGoogle Scholar
  60. 60.
    Roy S, Gupta S, Das S, Sekar K, Chatterji D, Vijayan M (2004) X-ray analysis of Mycobacterium smegmatis Dps and a comparative study involving other Dps and Dps-like molecules. J Mol Biol 339:1103–1113CrossRefPubMedGoogle Scholar
  61. 61.
    Frenkiel-Krispin D, Levin-Zaidman S, Shimoni E, Wolf SG, Wachtel EJ, Arad T, Finkel SE, Kolter R, Minsky A (2001) Regulated phase transitions of bacterial chromatin: a non-enzymatic pathway for generic DNA protection. EMBO J 20:1184–1191CrossRefPubMedGoogle Scholar
  62. 62.
    Wolf SG, Frenkiel D, Arad T, Finkel SE, Kolter R, Minsky A (1999) DNA protection by stress-induced biocrystallization. Nature 400:83–85CrossRefPubMedGoogle Scholar
  63. 63.
    Havukainen H, Haataja S, Kauko A, Pulliainen AT, Salminen A, Haikarainen T, Finne J, Papageorgiou AC (2008) Structural basis of the zinc- and terbium-mediated inhibition of ferroxidase activity in Dps ferritin-like proteins. Protein Sci 17:1513–1521CrossRefPubMedGoogle Scholar
  64. 64.
    Tsou CC, Chiang-Ni C, Lin YS, Chuang WJ, Lin MT, Liu CC, Wu JJ (2008) An iron-binding protein, Dpr, decreases hydrogen peroxide stress and protects Streptococcus pyogenes against multiple stresses. Infect Immun 76:4038–4045CrossRefPubMedGoogle Scholar
  65. 65.
    Li CQ, Soistman E, Carter DC (2006) Ferritin nanoparticle technology. A new platform for antigen presentation and vaccine development. Ind Biotechnol 2:143Google Scholar
  66. 66.
    Wu H, Wang J, Wang ZM, Fisher DR, Lin YH (2008) Apoferritin-templated yttrium phosphate nanoparticle conjugates for radioimmunotherapy of cancers. J Nanosci Nanotechnol 8:2316–2322CrossRefPubMedGoogle Scholar
  67. 67.
    Uchida M, Terashima M, Cunningham CH, Suzuki Y, Willits DA, Willis AF, Yang PC, Tsao PS, McConnell MV, Young MJ, Douglas T (2008) A human ferritin iron oxide nano-composite magnetic resonance contrast agent. Magn Reson Med 60:1073–1081CrossRefPubMedGoogle Scholar
  68. 68.
    Galvez N, Sanchez P, Dominguez-Vera JM (2005) Preparation of Cu and CuFe Prussian Blue derivative nanoparticles using the apoferritin cavity as nanoreactor. Dalton Trans7(15):2492–2494Google Scholar
  69. 69.
    Kramer RM, Sowards LA, Pender MJ, Stone MO, Naik RR (2005) Constrained iron catalysts for single-walled carbon nanotube growth. Langmuir 21:8466–8470CrossRefPubMedGoogle Scholar
  70. 70.
    Thieme D, Grass G (2009) The Dps protein of Escherichia coli is involved in copper homeostasis. Microbiol Res. doi:10.1016/j.micres.2008.12.003
  71. 71.
    Jeong K, Hung K, Baumler D, Byrd J, Kaspar C (2008) Acid stress damage of DNA is prevented by Dps binding in Escherichia coli O157:H7. BMC Microbiol 8:181CrossRefPubMedGoogle Scholar
  72. 72.
    Tonello F, Dundon WG, Satin B, Molinari M, Tognon G, Grandi G, Del Giudice G, Rappuoli R, Montecucco C (1999) The Helicobacter pylori neutrophil-activating protein is an iron-binding protein with dodecameric structure. Mol Microbiol 34:238–246CrossRefPubMedGoogle Scholar
  73. 73.
    Ceci P, Mangiarotti L, Rivetti C, Chiancone E (2007) The neutrophil-activating Dps protein of Helicobacter pylori, HP-NAP, adopts a mechanism different from Escherichia coli Dps to bind and condense DNA. Nucleic Acids Res 35:2247–2256CrossRefPubMedGoogle Scholar
  74. 74.
    Grove A, Wilkinson S (2005) Differential DNA binding and protection by dimeric and dodecameric forms of the ferritin homolog Dps from Deinococcus radiodurans. J Mol Biol 347:495–508CrossRefPubMedGoogle Scholar
  75. 75.
    Wiedenheft B, Mosolf J, Willits D, Yeager M, Dryden KA, Young M, Douglas T (2005) An archaeal antioxidant: characterization of a Dps-like protein from Sulfolobus solfataricus. Proc Natl Acad Sci USA 102:10551–10556CrossRefPubMedGoogle Scholar
  76. 76.
    Ceci P, Ilari A, Falvo E, Chiancone E (2003) The Dps protein of Agrobacterium tumefaciens does not bind to DNA but protects it toward oxidative cleavage: X-ray crystal structure, iron binding, and hydroxyl-radical scavenging properties. J Biol Chem 278:20319–20326CrossRefPubMedGoogle Scholar
  77. 77.
    Pulliainen AT, Haataja S, Kahkonen S, Finne J (2003) Molecular basis of H2O2 resistance mediated by Streptococcal Dpr. Demonstration of the functional involvement of the putative ferroxidase center by site-directed mutagenesis in Streptococcus suis. J Biol Chem 278:7996–8005CrossRefPubMedGoogle Scholar
  78. 78.
    Page RD (2002) Visualizing phylogenetic trees using TreeView. Curr Protoc Bioinformatics, chap 6, unit 6 2Google Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Teemu Haikarainen
    • 1
  • Anastassios C. Papageorgiou
    • 1
  1. 1.Turku Centre for BiotechnologyUniversity of Turku and Åbo Akademi UniversityTurkuFinland

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