Three-Dimensional Structure of Lactoferrin in Various Functional States

  • Edward N. Baker
  • Bryan F. Anderson
  • Heather M. Baker
  • Catherine L. Day
  • M. Haridas
  • Gillian E. Norris
  • Sylvia V. Rumball
  • Clyde A. Smith
  • David H. Thomas
Part of the Advances in, Experimental Medicine and Biology book series (AEMB, volume 357)

Summary

The three-dimensional structures of various forms of lactoferrin, determined by high resolution crystallographic studies, have been compared in order to determine the relationship between structure and biological function. These comparisons include human apo and diferric lactoferrins, metal and anion substituted lactoferrins, the N-terminal half molecule of human lactoferrin, and bovine diferric lactoferrin.

The structures themselves define the nature and location of the iron binding sites and allow anti-bacterial and putative receptor-binding regions to be mapped on to the molecular surface. The structural comparisons show that small internal adjustments can allow the accommodation of different metals and anions without altering the overall molecular structure, whereas large-scale conformational changes are associated with metal binding and release, and smaller, but significant, movements accompany species variations. The results also focus on differences in flexibility between the two lobes, and on the importance of interactions in the inter-lobe region in modulating iron release from the N-lobe and in possibly enabling binding at one site to be signalled to the other.

Keywords

Crystallization Carbohydrate Lymphoma Titration Carboxylate 

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References

  1. Aisen, P. and Harris, D.C. (1989). In Iron Carriers and Iron Proteins Loehr, T.M., ed. pp. 241–351, VCH Publishers, New York.Google Scholar
  2. Aisen P. and Leibman, A. (1972). Biochim. Biophys. Acta 257, 314–323.PubMedCrossRefGoogle Scholar
  3. Anderson, B.F., Baker, H.M., Dodson, E.J., Norris, G.E., Rumball, S.V., Waters, J.M. and Baker, E.N. (1987). Proc. Natl Acad. Sci. USA 84, 1769–1773.PubMedCrossRefGoogle Scholar
  4. Anderson, B.F., Baker, H.M., Norris, G.E., Rice, D.W. and Baker, E.N. (1989). J. Mol. Biol. 209, 711–734.PubMedCrossRefGoogle Scholar
  5. Anderson, B.F., Baker, H.M., Norris, G.E., Rumball, S.V. and Baker, E.N. (1990). Nature (London) 344, 784–787.CrossRefGoogle Scholar
  6. Arnold, R.R., Cole, M.F. and McGhee, J.R. (1977). Science 197, 263–265.PubMedCrossRefGoogle Scholar
  7. Baker, E.N. and Lindley, P.F. (1992). J. Inorg. Biochem. 47, 147–160.PubMedCrossRefGoogle Scholar
  8. Baker, E.N., Rumball, S.V. and Anderson, B.F. (1987) Trends in Biachem Sci. 12, 350–353.CrossRefGoogle Scholar
  9. Baker, E.N., Anderson, B.F., Baker, H.M., Haridas, M., Norris, G.E., Rumball, S.V. and Smith, C.A. (1990). Pure Appl. Chem. 62, 1067–1070.CrossRefGoogle Scholar
  10. Baker, E.N., Anderson, B.F., Baker, H.M., Haridas, M., Jameson, G.B., Norris, G.E., Rumball, S.V. and Smith, C.A. (1991) Int. J. Biol. Macromol. 13, 122–129.PubMedCrossRefGoogle Scholar
  11. Bali, P.K. and Aisen. P. (1991). Biochemistry 30, 9947–9952.PubMedCrossRefGoogle Scholar
  12. Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H., Kawase, K. and Tomita. M. (1992). Biochim. Biophys. Acta 1121, 130–136.PubMedCrossRefGoogle Scholar
  13. Birgens, H.S., Hansen, N.E., Karle, H. and Ostergaard Kristensen, L. (1983). Br. J. Haematol 54, 383–391.PubMedCrossRefGoogle Scholar
  14. Brock, J.H. (1985). In Metalloproteins (Harrison, P.M., ed.). Part 2, pp. 183–262, Macmillan, London.Google Scholar
  15. Bullen, J.J., Rogers, H.J., and Leigh, L. (1972). Brit Med. J. 3, 69–75.CrossRefGoogle Scholar
  16. Day, C.L., Stowell, K.M., Baker, E.N. and Tweedie, J.W. (1992).J. Biol. Chem. 267, 13857–13862.PubMedGoogle Scholar
  17. Grossmann, J.G., Neu, M., Pantos, E., Schwab, F.J., Evans, R.W., Townes-Andrews. E., Lindley, P.F., Appel, H., Thies, W-G and Hasnain, S.S. (1992). J. Mol. Biol. 225, 811–819.PubMedCrossRefGoogle Scholar
  18. Legrand, D., Mazurier, J., Colavizza, D., Montreuil, J. and Spik, G. (1990). Biochem. J. 266, 575–581.PubMedGoogle Scholar
  19. Mazurier, J. and Spik, G. (1980). Biochim. Biophys. Acta 629, 399–408.PubMedCrossRefGoogle Scholar
  20. Metz-Boutigue, M-H., Jolies, J., Mazurier, J., Schoentgen, F., Legrand, D., Spik, G. and Jolies, P. (1984). Eur. J. Biochem. 145, 659–676.PubMedCrossRefGoogle Scholar
  21. Norris, G.E., Baker, H.M. and Baker, E.N. (1989).J. Mol. Biol. 209, 329–331.PubMedCrossRefGoogle Scholar
  22. Quiocho, F.A. (1990). Phil. Trans. Roy. Soc. Lond. B326, 341–351.Google Scholar
  23. Rochard, E., Legrand, D., Mazurier, J., Montreuil, J. and Spik, G. (1989). FEBS Lett. 255, 201–204.PubMedCrossRefGoogle Scholar
  24. Shongwe, M.S., Smith, C.A., Ainscough, E.W., Baker, H.M., Brodie, A.M. and Baker. E.N. (1992). Biochemistry. 31, 4451–4458PubMedCrossRefGoogle Scholar
  25. Smith, C.A., Anderson, B.F., Baker, H.M. and Baker. E.N. (1992). Biochemistry 31, 4527–4533.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Edward N. Baker
    • 1
  • Bryan F. Anderson
    • 1
  • Heather M. Baker
    • 1
  • Catherine L. Day
    • 1
  • M. Haridas
    • 1
  • Gillian E. Norris
    • 1
  • Sylvia V. Rumball
    • 1
  • Clyde A. Smith
    • 1
  • David H. Thomas
    • 1
  1. 1.Department of Chemistry and BiochemistryMassey UniversityPalmerston NorthNew Zealand

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