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. 1994 Sep 15;302(Pt 3):813–820. doi: 10.1042/bj3020813

Iron incorporation into ferritins: evidence for the transfer of monomeric Fe(III) between ferritin molecules and for the formation of an unusual mineral in the ferritin of Escherichia coli.

E R Bauminger 1, A Treffry 1, A J Hudson 1, D Hechel 1, N W Hodson 1, S C Andrews 1, S Levi 1, I Nowik 1, P Arosio 1, J R Guest 1, et al.
PMCID: PMC1137303  PMID: 7945207

Abstract

Iron that has been oxidized by H-chain ferritin can be transferred into other ferritin molecules before it is incorporated into mature ferrihydrite iron cores. Iron(III) dimers are formed at the ferroxidase centres of ferritin H chains at an early stage of Fe(II) oxidation. Mössbauer spectroscopic data now show that the iron is transferred as monomeric species arising from dimer dissociation and that it binds to the iron core of the acceptor ferritin. Human H-chain ferritin variants containing altered threefold channels can act as acceptors, as can the ferritin of Escherichia coli (Ec-FTN). A human H-chain ferritin variant with a substituted tyrosine (rHuHF-Y34F) can act as a donor of Fe(III). Since an Fe(III)-tyrosinate (first identified in bullfrog H-chain ferritin) is absent from variant rHuHF-Y34F, the Fe(III) transferred is not derived from this tyrosinate complex. Mössbauer parameters of the small iron cores formed within Ec-FTN are significantly different from those of mammalian ferritins. Analysis of the spectra suggests that they are derived from both ferrihydrite and non-ferrihydrite components. This provides further evidence that the ferritin protein shell can influence the structure of its iron core.

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Selected References

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  1. Andrews S. C., Arosio P., Bottke W., Briat J. F., von Darl M., Harrison P. M., Laulhère J. P., Levi S., Lobreaux S., Yewdall S. J. Structure, function, and evolution of ferritins. J Inorg Biochem. 1992 Aug 15;47(3-4):161–174. doi: 10.1016/0162-0134(92)84062-r. [DOI] [PubMed] [Google Scholar]
  2. Arosio P., Adelman T. G., Drysdale J. W. On ferritin heterogeneity. Further evidence for heteropolymers. J Biol Chem. 1978 Jun 25;253(12):4451–4458. [PubMed] [Google Scholar]
  3. Bakker G. R., Boyer R. F. Iron incorporation into apoferritin. The role of apoferritin as a ferroxidase. J Biol Chem. 1986 Oct 5;261(28):13182–13185. [PubMed] [Google Scholar]
  4. Bauminger E. R., Harrison P. M., Hechel D., Hodson N. W., Nowik I., Treffry A., Yewdall S. J. Iron (II) oxidation and early intermediates of iron-core formation in recombinant human H-chain ferritin. Biochem J. 1993 Dec 15;296(Pt 3):709–719. doi: 10.1042/bj2960709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bauminger E. R., Harrison P. M., Hechel D., Nowik I., Treffry A. Iron (III) can be transferred between ferritin molecules. Proc Biol Sci. 1991 Jun 22;244(1311):211–217. doi: 10.1098/rspb.1991.0073. [DOI] [PubMed] [Google Scholar]
  6. Bauminger E. R., Harrison P. M., Hechel D., Nowik I., Treffry A. Mössbauer spectroscopic investigation of structure-function relations in ferritins. Biochim Biophys Acta. 1991 Dec 11;1118(1):48–58. doi: 10.1016/0167-4838(91)90440-b. [DOI] [PubMed] [Google Scholar]
  7. Bauminger E. R., Harrison P. M., Nowik I., Treffry A. Mössbauer spectroscopic study of the initial stages of iron-core formation in horse spleen apoferritin: evidence for both isolated Fe(III) atoms and oxo-bridged Fe(III) dimers as early intermediates. Biochemistry. 1989 Jun 27;28(13):5486–5493. doi: 10.1021/bi00439a025. [DOI] [PubMed] [Google Scholar]
  8. Chasteen N. D., Antanaitis B. C., Aisen P. Iron deposition in apoferritin. Evidence for the formation of a mixed valence binuclear iron complex. J Biol Chem. 1985 Mar 10;260(5):2926–2929. [PubMed] [Google Scholar]
  9. Cheesman M. R., le Brun N. E., Kadir F. H., Thomson A. J., Moore G. R., Andrews S. C., Guest J. R., Harrison P. M., Smith J. M., Yewdall S. J. Haem and non-haem iron sites in Escherichia coli bacterioferritin: spectroscopic and model building studies. Biochem J. 1993 May 15;292(Pt 1):47–56. doi: 10.1042/bj2920047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cheng Y. G., Chasteen N. D. Role of phosphate in initial iron deposition in apoferritin. Biochemistry. 1991 Mar 19;30(11):2947–2953. doi: 10.1021/bi00225a031. [DOI] [PubMed] [Google Scholar]
  11. Hanna P. M., Chen Y., Chasteen N. D. Initial iron oxidation in horse spleen apoferritin. Characterization of a mixed-valence iron(II)-iron(III) complex. J Biol Chem. 1991 Jan 15;266(2):886–893. [PubMed] [Google Scholar]
  12. Hudson A. J., Andrews S. C., Hawkins C., Williams J. M., Izuhara M., Meldrum F. C., Mann S., Harrison P. M., Guest J. R. Overproduction, purification and characterization of the Escherichia coli ferritin. Eur J Biochem. 1993 Dec 15;218(3):985–995. doi: 10.1111/j.1432-1033.1993.tb18457.x. [DOI] [PubMed] [Google Scholar]
  13. Lawson D. M., Artymiuk P. J., Yewdall S. J., Smith J. M., Livingstone J. C., Treffry A., Luzzago A., Levi S., Arosio P., Cesareni G. Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature. 1991 Feb 7;349(6309):541–544. doi: 10.1038/349541a0. [DOI] [PubMed] [Google Scholar]
  14. Lawson D. M., Treffry A., Artymiuk P. J., Harrison P. M., Yewdall S. J., Luzzago A., Cesareni G., Levi S., Arosio P. Identification of the ferroxidase centre in ferritin. FEBS Lett. 1989 Aug 28;254(1-2):207–210. doi: 10.1016/0014-5793(89)81040-3. [DOI] [PubMed] [Google Scholar]
  15. Le Brun N. E., Cheesman M. R., Thomson A. J., Moore G. R., Andrews S. C., Guest J. R., Harrison P. M. An EPR investigation of non-haem iron sites in Escherichia coli bacterioferritin and their interaction with phosphate. A study using nitric oxide as a spin probe. FEBS Lett. 1993 Jun 1;323(3):261–266. doi: 10.1016/0014-5793(93)81353-2. [DOI] [PubMed] [Google Scholar]
  16. Le Brun N. E., Wilson M. T., Andrews S. C., Guest J. R., Harrison P. M., Thomson A. J., Moore G. R. Kinetic and structural characterization of an intermediate in the biomineralization of bacterioferritin. FEBS Lett. 1993 Oct 25;333(1-2):197–202. doi: 10.1016/0014-5793(93)80404-i. [DOI] [PubMed] [Google Scholar]
  17. Levi S., Luzzago A., Cesareni G., Cozzi A., Franceschinelli F., Albertini A., Arosio P. Mechanism of ferritin iron uptake: activity of the H-chain and deletion mapping of the ferro-oxidase site. A study of iron uptake and ferro-oxidase activity of human liver, recombinant H-chain ferritins, and of two H-chain deletion mutants. J Biol Chem. 1988 Dec 5;263(34):18086–18092. [PubMed] [Google Scholar]
  18. Levi S., Salfeld J., Franceschinelli F., Cozzi A., Dorner M. H., Arosio P. Expression and structural and functional properties of human ferritin L-chain from Escherichia coli. Biochemistry. 1989 Jun 13;28(12):5179–5184. doi: 10.1021/bi00438a040. [DOI] [PubMed] [Google Scholar]
  19. Levi S., Yewdall S. J., Harrison P. M., Santambrogio P., Cozzi A., Rovida E., Albertini A., Arosio P. Evidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin. Biochem J. 1992 Dec 1;288(Pt 2):591–596. doi: 10.1042/bj2880591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Macara I. G., Hoy T. G., Harrison P. M. The formation of ferritin from apoferritin. Kinetics and mechanism of iron uptake. Biochem J. 1972 Jan;126(1):151–162. doi: 10.1042/bj1260151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Santambrogio P., Levi S., Arosio P., Palagi L., Vecchio G., Lawson D. M., Yewdall S. J., Artymiuk P. J., Harrison P. M., Jappelli R. Evidence that a salt bridge in the light chain contributes to the physical stability difference between heavy and light human ferritins. J Biol Chem. 1992 Jul 15;267(20):14077–14083. [PubMed] [Google Scholar]
  22. Sun S., Arosio P., Levi S., Chasteen N. D. Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants. Biochemistry. 1993 Sep 14;32(36):9362–9369. doi: 10.1021/bi00087a015. [DOI] [PubMed] [Google Scholar]
  23. Sun S., Chasteen N. D. Ferroxidase kinetics of horse spleen apoferritin. J Biol Chem. 1992 Dec 15;267(35):25160–25166. [PubMed] [Google Scholar]
  24. Treffry A., Bauminger E. R., Hechel D., Hodson N. W., Nowik I., Yewdall S. J., Harrison P. M. Defining the roles of the threefold channels in iron uptake, iron oxidation and iron-core formation in ferritin: a study aided by site-directed mutagenesis. Biochem J. 1993 Dec 15;296(Pt 3):721–728. doi: 10.1042/bj2960721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Treffry A., Harrison P. M., Cleton M. I., de Bruijn W. C., Mann S. A note on the composition and properties of ferritin iron cores. J Inorg Biochem. 1987 Sep;31(1):1–6. doi: 10.1016/0162-0134(87)85001-8. [DOI] [PubMed] [Google Scholar]
  26. Treffry A., Harrison P. M., Luzzago A., Cesareni G. Recombinant H-chain ferritins: effects of changes in the 3-fold channels. FEBS Lett. 1989 Apr 24;247(2):268–272. doi: 10.1016/0014-5793(89)81350-x. [DOI] [PubMed] [Google Scholar]
  27. Treffry A., Harrison P. M. Spectroscopic studies on the binding of iron, terbium, and zinc by apoferritin. J Inorg Biochem. 1984 May;21(1):9–20. doi: 10.1016/0162-0134(84)85035-7. [DOI] [PubMed] [Google Scholar]
  28. Treffry A., Harrison P. M. The binding of ferric iron by ferritin. Biochem J. 1979 Sep 1;181(3):709–716. doi: 10.1042/bj1810709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Treffry A., Hirzmann J., Yewdall S. J., Harrison P. M. Mechanism of catalysis of Fe(II) oxidation by ferritin H chains. FEBS Lett. 1992 May 11;302(2):108–112. doi: 10.1016/0014-5793(92)80417-f. [DOI] [PubMed] [Google Scholar]
  30. Wade V. J., Levi S., Arosio P., Treffry A., Harrison P. M., Mann S. Influence of site-directed modifications on the formation of iron cores in ferritin. J Mol Biol. 1991 Oct 20;221(4):1443–1452. doi: 10.1016/0022-2836(91)90944-2. [DOI] [PubMed] [Google Scholar]
  31. Wade V. J., Treffry A., Laulhère J. P., Bauminger E. R., Cleton M. I., Mann S., Briat J. F., Harrison P. M. Structure and composition of ferritin cores from pea seed (Pisum sativum). Biochim Biophys Acta. 1993 Jan 15;1161(1):91–96. doi: 10.1016/0167-4838(93)90201-2. [DOI] [PubMed] [Google Scholar]
  32. Waldo G. S., Ling J., Sanders-Loehr J., Theil E. C. Formation of an Fe(III)-tyrosinate complex during biomineralization of H-subunit ferritin. Science. 1993 Feb 5;259(5096):796–798. doi: 10.1126/science.8430332. [DOI] [PubMed] [Google Scholar]
  33. Watt R. K., Frankel R. B., Watt G. D. Redox reactions of apo mammalian ferritin. Biochemistry. 1992 Oct 13;31(40):9673–9679. doi: 10.1021/bi00155a021. [DOI] [PubMed] [Google Scholar]
  34. Yariv J., Kalb A. J., Sperling R., Bauminger E. R., Cohen S. G., Ofer S. The composition and the structure of bacterioferritin of Escherichia coli. Biochem J. 1981 Jul 1;197(1):171–175. doi: 10.1042/bj1970171. [DOI] [PMC free article] [PubMed] [Google Scholar]

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