The transfer of iron between ceruloplasmin and transferrins

Kenneth N. White, Celia Conesa, Lourdes Sánchez, Maryam Amini, Sebastien Farnaud, Chanakan Lorvoralak, Robert W. Evans

Research output: Contribution to journalReview article

22 Citations (Scopus)

Abstract

Background: It is over 60 years since the discovery and isolation of the serum ferroxidase ceruloplasmin. In that time much basic information about the protein has been elucidated including its catalytic and kinetic properties as an enzyme, expression, sequence and structure. The importance of its biological role is indicated in genetic diseases such as aceruloplasminemia where its function is lost through mutation. Despite this wealth of data, fundamental questions about its action remain unanswered and in this article we address the question of how ferric iron produced by the ferroxidase activity of ceruloplasmin could be taken up by transferrins or lactoferrins. Methods: Overlapping peptide libraries for human ceruloplasmin have been probed with a number of different lactoferrins to identify putative lactoferrin-binding regions on human ceruloplasmin. Docking software, 3D-Garden, has been used to model the binding of human lactoferrin to human ceruloplasmin. Results: Upon probing the human ceruloplasmin library with human lactoferrin, three predominantly acidic lactoferrin-binding peptides, located in domains 2, 5 and 6 of human ceruloplasmin, were identified. The docking software identified a complex such that the N-lobe of human apo-lactoferrin interacts with the catalytic ferroxidase centre on human ceruloplasmin. General Significance: In vitro binding studies and molecular modelling indicate that lactoferrin can bind to ceruloplasmin such that a direct transfer of ferric iron between the two proteins is possible. A direct transfer of ferric iron from ceruloplasmin to lactoferrin would prevent both the formation of potentially toxic hydroxyl radicals and the utilization of iron by pathogenic bacteria.

Original languageEnglish
Pages (from-to)411-416
Number of pages6
JournalBiochimica et Biophysica Acta - General Subjects
Volume1820
Issue number3
DOIs
Publication statusPublished - Mar 2012
Externally publishedYes

Keywords

  • Ceruloplasmin
  • Ferroxidase
  • Lactoferrin
  • Transferrin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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  • Cite this

    White, K. N., Conesa, C., Sánchez, L., Amini, M., Farnaud, S., Lorvoralak, C., & Evans, R. W. (2012). The transfer of iron between ceruloplasmin and transferrins. Biochimica et Biophysica Acta - General Subjects, 1820(3), 411-416. https://doi.org/10.1016/j.bbagen.2011.10.006