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Mechanisms of iron mineralization in ferritins: one size does not fit all

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Abstract

Significant progress has been made in recent years toward understanding the processes by which an iron mineral is deposited within members of the ferritin family of 24mer iron storage proteins, enabled by high-resolution structures together with spectroscopic and kinetic studies. These suggest common characteristics that are shared between ferritins, namely, a highly symmetric arrangement of subunits that provides a protein coat around a central cavity in which the mineral is formed, channels through the coat that facilitate ingress and egress of ions, and catalytic sites, called ferroxidase centers, that drive Fe2+ oxidation. They also reveal significant variations in both structure and mechanism amongst ferritins. Here, we describe three general types of structurally distinct ferroxidase center and the mechanisms of mineralization that they are associated with. The highlighted variation leads us to conclude that there is no universal mechanism by which ferritins function, but instead there exists several distinct mechanisms of ferritin iron mineralization.

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References

  1. Lewin A, Moore GR, Le Brun NE (2005) Dalton Trans 3597–3610

  2. Liu XF, Theil EC (2005) Acc Chem Res 38:167–175

    Article  CAS  PubMed  Google Scholar 

  3. Theil EC, Matzapetakis M, Liu XF (2006) J Biol Inorg Chem 11:803–810

    Article  CAS  PubMed  Google Scholar 

  4. Theil EC (2011) Curr Opin Chem Biol 15:304–311

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Le Brun NE, Thomson AJ, Moore GR (1997) In metal sites in proteins and models. Springer, Berlin, pp 103–138

    Book  Google Scholar 

  6. Aitken-Rogers H, Singleton C, Lewin A, Taylor-Gee A, Moore GR, Le Brun NE (2004) J Biol Inorg Chem 9:161–170

    Article  CAS  PubMed  Google Scholar 

  7. Ebrahimi HK, Bill E, Hagedoorn PL, Hagen WR (2012) Nat Chem Biol 8:941–948

    Article  Google Scholar 

  8. Le Brun NE, Crow A, Murphy MEP, Mauk AG, Moore GR (2010) Biochim Biophys Acta 1800:732–744

    Article  PubMed  Google Scholar 

  9. Tosha T, Ng HL, Bhattasali O, Alber T, Theil EC (2010) J Am Chem Soc 132:14562–14569

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Levi S, Santambrogio P, Corsi B, Cozzi A, Arosio P (1996) Biochem J 317:467–473

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Haldar S, Bevers LE, Tosha T, Theil EC (2011) J Biol Chem 286:25620–25627

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Liu XF, Jin WL, Theil EC (2003) Proc Natl Acad Sci USA 100:3653–3658

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Masuda T, Goto F, Yoshihara T, Mikami B (2010) J Biol Chem 285:4049–4059

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Macedo S, Romao CV, Mitchell E, Matias PM, Liu MY, Xavier AV, LeGall J, Teixeira M, Lindley P, Carrondo MA (2003) Nat Struct Biol 10:285–290

    Article  CAS  PubMed  Google Scholar 

  15. Chasteen ND, Harrison PM (1999) J Struct Biol 126:182–194

    Article  CAS  PubMed  Google Scholar 

  16. Harrison PM, Arosio P (1996) Biochim Biophys Acta 1275:161–203

    Article  PubMed  Google Scholar 

  17. Li C, Hu X, Zhao G (2009) Biochimie 91:230–239

    Article  CAS  PubMed  Google Scholar 

  18. Andrews SC (2010) Biochim Biophys Acta 1800:691–705

    Article  CAS  PubMed  Google Scholar 

  19. Abdul-Tehrani H, Hudson AJ, Chang YS, Timms AR, Hawkins C, Williams JM, Harrison PM, Guest JR, Andrews SC (1999) J Bacteriol 181:1415–1428

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Bertini I, Lalli D, Mangani S, Pozzi C, Rosa C, Theil EC, Turano P (2012) J Am Chem Soc 134:6169–6176

    Article  CAS  PubMed  Google Scholar 

  21. Lawson DM, Artymiuk PJ, Yewdall SJ, Smith JMA, Livingstone JC, Treffry A, Luzzago A, Levi S, Arosio P, Cesareni G, Thomas CD, Shaw WV, Harrison PM (1991) Nature 349:541–544

    Article  CAS  PubMed  Google Scholar 

  22. Le Brun NE, Wilson MT, Andrews SC, Guest JR, Harrison PM, Thomson AJ, Moore GR (1993) FEBS Lett 333:197–202

    Article  PubMed  Google Scholar 

  23. Hamburger AE, West AP, Hamburger ZA, Hamburger P, Bjorkman PJ (2005) J Mol Biol 349:558–569

    Article  CAS  PubMed  Google Scholar 

  24. Toussaint L, Bertrand L, Hue L, Crichton RR, Declercq JP (2007) J Mol Biol 365:440–452

    Article  CAS  PubMed  Google Scholar 

  25. Chen-Barrett Y, Harrison PM, Treffry A, Quail MA, Arosio P, Santambrogio P, Chasteen ND (1995) Biochemistry 34:7847–7853

    Article  CAS  PubMed  Google Scholar 

  26. Hempstead PD, Hudson AJ, Artymiuk PJ, Andrews SC, Banfield MJ, Guest JR, Harrison PM (1994) FEBS Lett 350:258–262

    Article  CAS  PubMed  Google Scholar 

  27. Stillman TJ, Hempstead PD, Artymiuk PJ, Andrews SC, Hudson AJ, Treffry A, Guest JR, Harrison PM (2001) J Mol Biol 307:587–603

    Article  CAS  PubMed  Google Scholar 

  28. Tatur J, Hagen WR, Matias PM (2007) J Biol Inorg Chem 12:615–630

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Johnson E, Cascio D, Sawaya MR, Gingery M, Schroder I (2005) Structure 13:637–648

    Article  CAS  PubMed  Google Scholar 

  30. Marchetti A, Parker MS, Moccia LP, Lin EO, Arrieta AL, Ribalet F, Murphy MEP, Maldonado MT, Armbrust EV (2009) Nature 457:467–470

    Article  CAS  PubMed  Google Scholar 

  31. Pfaffen S, Abdulqadir R, Le Brun NE, Murphy ME (2013) J Biol Chem 288:14917–14925

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Andrews SC, Le Brun NE, Barynin V, Thomson AJ, Moore GR, Guest JR, Harrison PM (1995) J Biol Chem 270:23268–23274

    Article  CAS  PubMed  Google Scholar 

  33. Frolow F, Kalb AJ, Yariv J (1994) Nat Struct Biol 1:453–460

    Article  CAS  PubMed  Google Scholar 

  34. Yasmin S, Andrews SC, Moore GR, Le Brun NE (2011) J Biol Chem 286:3473–3483

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Crow A, Lawson TL, Lewin A, Moore GR, Le Brun NE (2009) J Am Chem Soc 131:6808–6813

    Article  CAS  PubMed  Google Scholar 

  36. Swartz L, Kuchinskas M, Li HY, Poulos TL, Lanzilotta WN (2006) Biochemistry 45:4421–4428

    Article  CAS  PubMed  Google Scholar 

  37. Weeratunga SK, Lovell S, Yao H, Battaile KP, Fischer CJ, Gee CE, Rivera M (2010) Biochemistry 49:1160–1175

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Nordlund P, Sjoberg BM, Eklund H (1990) Nature 345:593–598

    Article  CAS  PubMed  Google Scholar 

  39. Rosenzweig AC, Frederick CA, Lippard SJ, Nordlund P (1993) Nature 366:537–543

    Article  CAS  PubMed  Google Scholar 

  40. Jameson GNL, Jin W, Krebs C, Perreira AS, Tavares P, Liu XF, Theil EC, Huynh BH (2002) Biochemistry 41:13435–13443

    Article  CAS  PubMed  Google Scholar 

  41. Zhao GH, Bou-Abdallah F, Arosio P, Levi S, Janus-Chandler C, Chasteen ND (2003) Biochemistry 42:3142–3150

    Article  CAS  PubMed  Google Scholar 

  42. Bou-Abdallah F, Papaefthymiou GC, Scheswohl DM, Stanga SD, Arosio P, Chasteen ND (2002) Biochem J 364:57–63

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Pereira AS, Small W, Krebs C, Tavares P, Edmondson DE, Theil EC, Huynh BH (1998) Biochemistry 37:9871–9876

    Article  CAS  PubMed  Google Scholar 

  44. Moenne-Loccoz P, Krebs C, Herlihy K, Edmondson DE, Theil EC, Huynh BH, Loehr TM (1999) Biochemistry 38:5290–5295

    Article  CAS  PubMed  Google Scholar 

  45. Bou-Abdallah F, Zhao GH, Mayne HR, Arosio P, Chasteen ND (2005) J Am Chem Soc 127:3885–3893

    Article  CAS  PubMed  Google Scholar 

  46. Zhao GH, Su MH, Chasteen ND (2005) J Mol Biol 352:467–477

    Article  CAS  PubMed  Google Scholar 

  47. Zhao ZW, Treffry A, Quail MA, Guest JR, Harrison PM (1997) Dalton Trans 3977–3978

  48. Treffry A, Zhao Z, Quail MA, Guest JR, Harrison PM (1995) Biochemistry 34:15204–15213

    Article  CAS  PubMed  Google Scholar 

  49. Yang XK, Chen-Barrett Y, Arosio P, Chasteen ND (1998) Biochemistry 37:9743–9750

    Article  CAS  PubMed  Google Scholar 

  50. Bauminger ER, Harrison PM, Hechel D, Nowik I, Treffry A (1993) Nucl Instr Meth Phys Res B 76:403–404

    Article  Google Scholar 

  51. Pereira AS, Tavares P, Lloyd SG, Danger D, Edmondson DE, Theil EC, Huynh BH (1997) Biochemistry 36:7917–7927

    Article  CAS  PubMed  Google Scholar 

  52. Waldo GS, Theil EC (1993) Biochemistry 32:13262–13269

    Article  CAS  PubMed  Google Scholar 

  53. Turano P, Lalli D, Felli IC, Theil EC, Bertini I (2010) Proc Natl Acad Sci USA 107:545–550

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Xu B, Chasteen ND (1991) J Biol Chem 266:19965–19970

    CAS  PubMed  Google Scholar 

  55. Treffry A, Zhao ZW, Quail MA, Guest JR, Harrison PM (1998) FEBS Lett 432:213–218

    Article  CAS  PubMed  Google Scholar 

  56. Bou-Abdallah F, Yang H, Awomolo A, Cooper B, Woodhall MR, Andrews SC, Chasteen ND (2014) Biochemistry 53:483–495

    Article  CAS  PubMed  Google Scholar 

  57. Bauminger ER, Treffry A, Quail MA, Zhao ZW, Nowik I, Harrison PM (1999) Biochemistry 38:7791–7802

    Article  CAS  PubMed  Google Scholar 

  58. Bauminger ER, Treffry A, Quail MA, Zhao ZW, Nowik I, Harrison PM (2000) Inorg Chim Acta 297:171–180

    Article  CAS  Google Scholar 

  59. Ebrahimi KH, Hagedoorn PL, Jongejan JA, Hagen WR (2009) J Biol Inorg Chem 14:1265–1274

    Article  Google Scholar 

  60. Ebrahimi KH, Hagedoorn PL, Hagen WR (2013) Chembiochem 14:1123–1133

    Article  CAS  PubMed  Google Scholar 

  61. Yang X, Le Brun NE, Thomson AJ, Moore CR, Chasteen ND (2000) Biochemistry 39:4915–4923

    Article  CAS  PubMed  Google Scholar 

  62. Bou-Abdallah F, Lewin AC, Le Brun NE, Moore GR, Chasteen ND (2002) J Biol Chem 277:37064–37069

    Article  CAS  PubMed  Google Scholar 

  63. Baaghil S, Lewin A, Moore GR, Le Brun NE (2003) Biochemistry 42:14047–14056

    Article  CAS  PubMed  Google Scholar 

  64. Lawson TL, Crow A, Lewin A, Yasmin S, Moore GR, Le Brun NE (2009) Biochemistry 48:9031–9039

    Article  CAS  PubMed  Google Scholar 

  65. Le Brun NE, Andrews SC, Guest JR, Harrison PM, Moore GR, Thomson AJ (1995) Biochem J 312:385–392

    PubMed Central  PubMed  Google Scholar 

  66. Watt GD, Frankel RB, Jacobs D, Huang HQ (1992) Biochemistry 31:5672–5679

    Article  CAS  PubMed  Google Scholar 

  67. Wong SG, Tom-Yew SAL, Lewin A, Le Brun NE, Moore GR, Murphy MEP, Mauk AG (2009) J Biol Chem 284:18873–18881

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. DeLano WL (2002) The PyMOL molecular graphics system. DeLano Scientific, San Carlos

    Google Scholar 

Download references

Acknowledgments

We thank the UK’s BBSRC for supporting our work on ferritins through Grant BB/I021884/1.

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  1. School of Chemistry, Centre for Molecular and Structural Biochemistry, University of East Anglia, Norwich, NR4 7TJ, UK

    Justin M. Bradley, Geoffrey R. Moore & Nick E. Le Brun

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  1. Justin M. Bradley
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  2. Geoffrey R. Moore
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  3. Nick E. Le Brun
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Correspondence to Nick E. Le Brun.

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Bradley, J.M., Moore, G.R. & Le Brun, N.E. Mechanisms of iron mineralization in ferritins: one size does not fit all. J Biol Inorg Chem 19, 775–785 (2014). https://doi.org/10.1007/s00775-014-1136-3

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