Skip to main content
SpringerLink
Log in

DNA and oligosaccharides stimulate oligomerization of human milk lactoferrin

  • Structural-Functional Analysis of Biopolymers and Their Complexes
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Lactoferrin (LF) is a Fe3+-transferring glycoprotein and is contained in human barrier fluids, blood, and milk. LF is an acute phase protein, is involved in nonspecific defense, and displays a unique set of biological functions. Small-angle X-ray scattering and light scattering experiments demonstrated that DNA and oligosaccharides added to LF with various levels of initial oligomerization increased the oligomerization rate. Almost complete dissociation into monomers was observed when 1 M NaCl was added to LF oligomers obtained in the presence of DNA, oligosaccharides, and nucleotides, previously identified as oligomerization effectors. LF complexes obtained with different oligomerization effectors differed in stability. Incubation with 50 mM MgCl2 completely destructed LF complexes formed in the presence of ATP and oligosaccharides but only partly destructed AMP- and d(pT)10-dependent complexes, which was followed by the formation of new complexes with a higher salt stability. A possible role of oligomerization in various LF functions is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anderson B., Baker H., Norris G., Rice D., Baker E. 1989. Structure of human lactoferrin: Crystallographic structure analysis and refinement at 2.8 Å resolution. J. Mol. Biol. 209, 711–734.

    Article  PubMed  CAS  Google Scholar 

  2. van Berkel P., van Veen H., Geerts M., de Boer H., Nuijens J. 1996. Heterogeneity in utilization of N-glycosylation sites Asn624 and Asn138 in human lactoferrin: A study with glycosylation-site mutants. Biochem. J. 319, 117–122.

    PubMed  Google Scholar 

  3. Sousa M., Brock J. 1989. Iron in immunity. Cancer and Inflammation. N.Y.: Wiley.

    Google Scholar 

  4. Birgens H. 1985. Lactoferrin in plasma measured by an ELISA technique: evidence that plasma lactoferrin is an indicator of neutrophil turnover and bone marrow activity in acute leukemia. Scand. J. Haematol. 34, 326–331.

    PubMed  CAS  Google Scholar 

  5. Levay P., Viljoen M. 1995. Lactoferrin: A general review. Haematologica. 80, 252–267.

    PubMed  CAS  Google Scholar 

  6. Kanyshkova T.G., Buneva V.N., Nevinsky G.A. 2001. Lactoferrin and its biological functions. Biokhimiya. 66, 5–13.

    Google Scholar 

  7. Chapple D.S., Mason D.J., Joannou C.L., Odell E.W., Gant V., Evans R.W. 1998. Infect. Immun. 66, 2434–2440.

    PubMed  CAS  Google Scholar 

  8. van der Strate B.W., Beljaars L., Molema G., Harmsen M.C., Meijer D.K. 2001. Antiviral activities of lactoferrin. Antiviral. Res. 52, 225–239.

    Article  PubMed  Google Scholar 

  9. Kijlstra A. 1990. The role of lactoferrin in the nonspecific immune response on the ocular surface. Reg. Immunol. 3, 193–197.

    PubMed  Google Scholar 

  10. Zhang W., Lachmann P.J. 1996. Neutrophil lactoferrin release induced by IgA immune complexes can be mediated either by Fc α receptors or by complement receptors through different pathways. J. Immunol. 156, 2599–2606.

    PubMed  CAS  Google Scholar 

  11. Bagby G.C. Jr. 1989. Regulation of granulopoiesis: The lactoferrin controversy. Blood Cells. 15, 386–399.

    PubMed  CAS  Google Scholar 

  12. Nishiya K., Horwitz D.A. 1982. Contrasting effects of lactoferrin on human lymphocyte and monocyte natural killer activity and antibody-dependent cell-mediated cytotoxicity. J. Immunol. 129, 2519–2523.

    PubMed  CAS  Google Scholar 

  13. Rejman J.J., Turner J.D., Oliver S.P. 1994. Characterization of lactoferrin binding to the MAC-T bovine mammary epithelial cell line using a biotin-avidin technique. Int. J. Biochem. 26, 201–206.

    Article  PubMed  CAS  Google Scholar 

  14. Ziere G.J., Bijsterbosch M.K., van Berkel T.J.C. 1993. Removal of 14 N-terminal amino acids of lactoferrin enhances its affinity for parenchymal liver cells and potentiates the inhibition of β-very low density lipoprotein binding. J. Biol. Chem. 268, 27069–27075.

    PubMed  CAS  Google Scholar 

  15. Tsuda H., Sekine K., Fujita K., Ligo M. 2002. Cancer prevention by bovine lactoferrin and underlying mechanisms: A review of experimental and clinical studies. Biochem. Cell Biol. 80, 131–136.

    Article  PubMed  CAS  Google Scholar 

  16. Yoo Y.C., Watanabe R., Koike Y., Mitobe M., Shimazaki K., Watanabe S., Azuma I. 1997. Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk protein-derived peptide: Involvement of reactive oxygen species. Biochem. Biophys. Res. Commun. 237, 624–628.

    Article  PubMed  CAS  Google Scholar 

  17. van Berkel P.H., Geerts M.E., van Veen H.A., Mericskay M., de Boier H., Nuijens J.H. 1997. N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme and DNA. Biochem. J. 328, 145–151.

    PubMed  Google Scholar 

  18. Bennett R.M., Davis J. 1982. Lactoferrin interacts with deoxyribonucleic acid: A preferential reactivity with double-stranded DNA and dissociation of DNA-anti-DNA complexes. J. Lab. Clin. Med. 99, 127–138.

    PubMed  CAS  Google Scholar 

  19. He J., Furmanski P. 1995. Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA. Nature. 373(6516), 721–724.

    Article  PubMed  CAS  Google Scholar 

  20. Fleet J. 1995. A new role for lactoferrin: DNA binding and transcription activation. Nutr. Rev. 53, 226–227.

    Article  PubMed  CAS  Google Scholar 

  21. Furmanski P., Li Z., Fortuna M., Swamy C., Das M. 1989. Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity. J. Exp. Med. 170, 415–429.

    Article  PubMed  CAS  Google Scholar 

  22. Kanyshkova T., Babina S., Semenov D., Isaeva N., Vlassov A., Neustroev K., Kul’minskaya A., Buneva V., Nevinsky G. 2003. Multiple enzymic activities of human milk lactoferrin. Eur. J. Biochem. 270, 3353–3361.

    Article  PubMed  CAS  Google Scholar 

  23. Babina E.S., Semenov D.I., Buneva V.N., Nevinsky G.A. 2005. Human milk lactoferrin hydrolyzes ribonucleoside 5′-triphosphates. Mol. Biol. 39, 513–520.

    Article  CAS  Google Scholar 

  24. Semenov D., Kanyshkova T., Buneva V., Nevinsky G. 1999. Human milk lactoferrin binds ATP and dissociates into monomers. Biochem. Mol. Biol. Int. 47, 177–184.

    PubMed  CAS  Google Scholar 

  25. Babina S., Nevinsky G. 2004. Lactoferrin interacts with nucleotides. Nucleosides Nucleotides Nucleic Acids. 23, 1043–1046.

    Article  PubMed  CAS  Google Scholar 

  26. Mantel C., Miyazawa K., Broxmeyer H. 1994. Physical characteristics and polymerization during iron saturation of lactoferrin, a myelopoietic regulatory molecule with suppressor activity. Adv. Exp. Med. Biol. 357, 121–132.

    PubMed  CAS  Google Scholar 

  27. Bagby G., Bennet R. 1982. Feedback regulation of granulopoiesis: Polymerization of lactoferrin abrogates its ability to inhibit CSA production. Blood. 60, 108–112.

    PubMed  CAS  Google Scholar 

  28. Babina S.E., Tuzikov F.V., Tuzikova N.A., Buneva V.N., Nevinsky G.A. 2006. Effect of nucleotides on the oligomeric state of human lactoferrin. Mol. Biol. 40, 137–150.

    Article  CAS  Google Scholar 

  29. Babina S.E., Kanyshkova T.G., Buneva V.N., Nevinsky G.A. 2004. Lactoferrin: A major deoxyribonuclease in human milk. Biokhimiya. 69, 1239–1250.

    Google Scholar 

  30. Svergun D.I., Feigin L.A. 1986. Rentgenovskoe i neitronnoe malouglovoe rasseyanie (Small Angle X-Ray and Neutron Scattering), Moscow: Nauka, pp. 50–279.

    Google Scholar 

  31. Fersht A. 1985. Enzyme Structure and Mechanism. N.Y.: Freeman.

    Google Scholar 

  32. Kanyshkova T., Semenov D., Buneva V., Nevinsky G. 1999. Human milk lactoferrin binds two DNA molecules with different affinities. FEBS Lett. 451, 235–237.

    Article  PubMed  CAS  Google Scholar 

  33. Anderson B.F., Baker H.M., Norris G.E., Rice D.W., Baker E.N. 1989. Structure of human lactoferrin: Crystallographic structure analysis and refinement at 2.8 Å resolution. J. Mol. Biol. 209, 711–734.

    Article  PubMed  CAS  Google Scholar 

  34. Nevinsky G., Babina S. 2003. Human milk lactoferrin and its polyfunctional biological functions. In: Protein Structures. Kaleidoscope of Structural Properties and Functions. Ed. Uversky V.N. India: Research Signpost, vol. 5, pp. 499–530.

    Google Scholar 

  35. Watanabe T., Nagura H., Watanabe K., Brown W. 1984. The binding of human milk lactoferrin to immunoglobulin A. FEBS Lett. 168, 203–207.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    S. E. Soboleva (Babina), V. N. Buneva & G. A. Nevinsky

  2. Boreskov Institute of Catalysis, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    F. V. Tuzikov & N. A. Tuzikova

  3. Novosibirsk State University, Novosibirsk, 630090, Russia

    S. E. Soboleva (Babina), V. N. Buneva & G. A. Nevinsky

Authors
  1. S. E. Soboleva (Babina)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. V. Tuzikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. A. Tuzikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. N. Buneva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. A. Nevinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. A. Nevinsky.

Additional information

Original Russian Text © S.E. Soboleva (Babina), F.V. Tuzikov, N.A Tuzikova, V.N. Buneva, G.A. Nevinsky, 2009, published in Molekulyarnaya Biologiya, 2009, Vol. 43, No. 1, pp. 157–165.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Soboleva (Babina), S.E., Tuzikov, F.V., Tuzikova, N.A. et al. DNA and oligosaccharides stimulate oligomerization of human milk lactoferrin. Mol Biol 43, 142–149 (2009). https://doi.org/10.1134/S0026893309010191

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893309010191

Key words

Search

Navigation