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Absence of Binding Between the Human Transferrin Receptor and the Transferrin Complex of Biological Toxic Trace Element, Aluminum, Because of an Incomplete Open/Closed Form of the Complex

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Abstract

Human transferrin (Tf) very tightly binds two ferric ions to deliver iron to cells. Fe(III)2Tf (Fe2Tf) binds to the Tf receptor (TfR) at pH 7.4; however, iron-free Tf (apoTf) does not. Iron uptake is facilitated by endocytosis of the Fe2Tf–TfR complex. Tf can also bind aluminum ions, which cause toxic effects and are associated with many diseases. Since Al(III)2Tf (Al2Tf) does not bind to TfR, the uptake of aluminum by the cells does not occur through a TfR-mediated pathway. We have studied the absence of binding between Al2Tf and TfR by investigating the physicochemical characteristics of apoTf, Al2Tf, Fe2Tf, and TfR. The hydrodynamic radius of 38.8 Å for Al2Tf obtained by dynamic light scattering was between that of 42.6 Å for apoTf and 37.2 Å for Fe2Tf. The ζ potential of −11.3 mV for Al2Tf measured by capillary electrophoresis was close to −11.2 mV for apoTf as compared to −11.9 mV for Fe2Tf, indicating that the Al2Tf surface had a relatively scarce negative charge as the apoTf surface had. These results demonstrated that the structure of Al2Tf was a trade-off between the closed and open forms of Fe2Tf and apoTf, respectively. Consequently, it is suggested that Al2Tf cannot form specific ionic interresidual interactions, such as those formed by Fe2Tf, to bind to TfR, resulting in impossible complex formation between Al2Tf and TfR.

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Authors and Affiliations

  1. Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku, 162-8601, Tokyo, Japan

    Tetsuya Sakajiri & Hirofumi Yajima

  2. Department of Food and Nutrition, Morioka Junior College, 808 Sunagome, Takizawa, Iwate, 020-0183, Japan

    Tetsuya Sakajiri, Takaki Yamamura & Takako Sawada

  3. Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, 525-8577, Shiga, Japan

    Takeshi Kikuchi

  4. Department of Biochemistry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, 321-0293, Tochigi, Japan

    Kaoru Ichimura

Authors
  1. Tetsuya Sakajiri
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  2. Takaki Yamamura
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  3. Takeshi Kikuchi
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  4. Kaoru Ichimura
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  5. Takako Sawada
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  6. Hirofumi Yajima
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Correspondence to Takaki Yamamura.

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Sakajiri, T., Yamamura, T., Kikuchi, T. et al. Absence of Binding Between the Human Transferrin Receptor and the Transferrin Complex of Biological Toxic Trace Element, Aluminum, Because of an Incomplete Open/Closed Form of the Complex. Biol Trace Elem Res 136, 279–286 (2010). https://doi.org/10.1007/s12011-009-8547-y

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  • DOI: https://doi.org/10.1007/s12011-009-8547-y

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