Letter | Published:

Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts

Abstract

FERRITINis important in iron homeostasis. Its twenty-four chains of two types, H and L, assemble as a hollow shell providing an iron-storage cavity1–3. Ferritin molecules in cells containing high levels of iron tend to be rich in L chains, and may have a long-term storage function, whereas H-rich ferritins are more active in iron metabolism3–7. The molecular basis for the greater activity of H-rich ferritins has until now been obscure, largely because the structure of H-chain ferritin has remained unknown owing to the difficulties in obtaining crystals ordered enough for X-ray crys-tallographic analysis. Here we report the three-dimensional structure of a human ferritin H-chain homopolymer. By genetically engineering a change in the sequence of the intermolecular contact region, we obtained crystals isomorphous with the homologous rat L ferritin8–9 and of high enough quality for X-ray diffraction analysis. The X-ray structure of human H ferritin shows a novel metal site embedded within each of its four-helix bundles and we suggest that ferroxidase activity associated with this site accounts for its rapid uptake of iron10.

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References

  1. 1

    Ford, G. C. et al. Phil. Trans. R. Soc. Lond. B304, 551–565 (1984).

  2. 2

    Harrison, P. M. et al. in Biomineralisation: Chemical and Biochemical Perspective (eds. Mann, S., Webb, J. & Williams, R. J. P.) 257–294 (VCH Verlagsgesellschaft, Weinheim, 1989).

  3. 3

    Arosio, P., Adelman, T. G. & Drysdale, J. W. J. biol. Chem. 253, 4451–4458 (1978).

  4. 4

    Theil, E. C. A. Rev. Biochem. 56, 289–315 (1987).

  5. 5

    Levi, S. et al. J. biol. Chem. 263, 18086–18092 (1988).

  6. 6

    Arosio, P., Gatti, G. & Bolognesi, M. Biochim. biophys. Acta 774, 230–232 (1983).

  7. 7

    Levi, S. et al. Biochemistry 28, 5179–5184 (1989).

  8. 8

    Lawson, D. M., thesis, Sheffield Univ. (1990).

  9. 9

    Thomas, C. D. et al. Biochem. Soc. Trans. 16, 838–839 (1988).

  10. 10

    Lawson, D. M. et al. FEBS Lett. 254, 207–210 (1989).

  11. 11

    Banyard, S. H., Stammers, D. K. & Harrison, P. M. Nature 271, 282–284 (1978).

  12. 12

    Treffry, A., Harrison, P. M., Luzzago, A. & Cesareni, G. FEBS Lett. 247, 268–272 (1989).

  13. 13

    Levi, S. et al. Biochem. J. 264, 381–388 (1989).

  14. 14

    Bakker, G. R. & Boyer, R. F. J. biol. Chem. 261, 13182–13185 (1986).

  15. 15

    Connolly, M. L. J. appl. Cryst. 16, 23–28 (1983).

  16. 16

    Treffry, A. & Harrison, P. M. J. inorg. Biochem. 21, 9–20 (1984).

  17. 17

    Bauminger, E. R., Harrison, P. M., Nowik, I. & Treffry, A. Biochemistry 25, 5486–5493 (1989).

  18. 18

    Chasteen, N. D. & Theil, E. C. J. biol. Chem. 257, 7672–7677 (1982).

  19. 19

    Stenkamp, R. E., Sieker, L. C. & Jensen, L. H. J. Am. Chem. Soc. 106, 618–622 (1984).

  20. 20

    Sheriff, S., Hendrickson, W. A. & Smith, J. L. J. molec. Biol. 197, 273–296 (1987).

  21. 21

    Nordlund, P., Sjöberg, B-M. & Eklund, H. Nature 345, 593–598 (1990).

  22. 22

    Konnert, J. H. & Hendrickson, W. A. Acta crystallogr. A36, 344–350 (1980).

  23. 23

    Fraser, R. D. B., MacRae, T. P. & Suzuki, E. J. appl. Cryst. 11, 693–694 (1978).

  24. 24

    Boyd, D., Vecoli, C., Belcher, D. M., Jain, S. K. & Drysdale, J. W. J. biol. Chem. 260, 11755–11761 (1985).

  25. 25

    Murray, M. J., White, K. & Munro, H. N. Proc. natn. Acad. Sci. U.S.A. 84, 7438–7442 (1987).

  26. 26

    Stevens, P. W., Dodgson, J. B. & Engel, J. D. Molec. cell. Biol. 7, 1751–1758 (1987).

  27. 27

    Dickey, L. F. et al. J. biol. Chem. 262, 7901–7907 (1987).

  28. 28

    Leibold, E. A. & Munro, H. N. J. biol. Chem. 262, 7335–7341 (1987).

  29. 29

    Heusterspreute, M. & Crichton, R. R. FEBS Letts 129, 322–327 (1981).

  30. 30

    Daniels-McQueen, S. et al. Nucleic Acids Res. 16, 7741 (1988).

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