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Large cooperativity in the removal of iron from transferrin at physiological temperature and chloride ion concentration

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Abstract

Iron removal from serum transferrin by various chelators has been studied by gel electrophoresis, which allows direct quantitation of all four forms of transferrin (diferric, C-monoferric, N-monoferric, and apotransferrin). Large cooperativity between the two lobes of serum transferrin is found for iron removal by several different chelators near physiological conditions (pH 7.4, 37 °C, 150 mM NaCl, 20 mM NaHCO3). This cooperativity is manifested in a dramatic decrease in the rate of iron removal from the N-monoferric transferrin as compared with iron removal from the other forms of ferric transferrin. Cooperativity is diminished as the pH is decreased; it is also very sensitive to changes in chloride ion concentration, with a maximum cooperativity at 150 mM NaCl. A mechanism is proposed that requires closure of the C-lobe before iron removal from the N-lobe can be effected; the “open” conformation of the C-lobe blocks a kinetically significant anion-binding site of the N-lobe, preventing its opening. Physiological implications of this cooperativity are discussed.

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Acknowledgements

This research was supported by NIH grant DK 57814. We thank Emily Dertz for helpful discussions.

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  1. Department of Chemistry, University of California, Berkeley, CA , 94720, USA

    David H. Hamilton, Isabelle Turcot, Alain Stintzi & Kenneth N. Raymond

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  1. David H. Hamilton
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  2. Isabelle Turcot
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Correspondence to Kenneth N. Raymond.

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Hamilton, D.H., Turcot, I., Stintzi, A. et al. Large cooperativity in the removal of iron from transferrin at physiological temperature and chloride ion concentration. J Biol Inorg Chem 9, 936–944 (2004). https://doi.org/10.1007/s00775-004-0592-6

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  • DOI: https://doi.org/10.1007/s00775-004-0592-6

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