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Electrostatic interactions in the assembly of haemoglobin

Nature volume 306, pages 498–500 (1983)Cite this article

Abstract

Haemoglobin is the prototype of an allosteric protein in which cooperative behaviour depends on interaction between unlike subunits1–3. Here we present haematological and biochemical evidence that electrostatic interactions are an important determinant of haemoglobin assembly. Individuals heterozygous for positively charged β-globin variants have a significantly lower proportion of abnormal haemoglobin than those with negatively charged variants. Moreover, these differences become more pronounced when α-thalassaemia is also present. Kinetic experiments using isolated chains indicate that the rate of assembly of the heterotetramer is influenced by alterations in surface charge. A simple electrostatic model is proposed in an attempt to explain these haematological and experimental findings.

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References

  1. Perutz, M. F. Nature 228, 726–733 (1970).

    Article  ADS  CAS  Google Scholar 

  2. Benesch, R. & Benesch, R. E. Science 185, 905–908 (1974).

    Article  ADS  CAS  Google Scholar 

  3. Antonini, E., Bucci, E., Fronticelli, C., Wyman, J. & Rossi-Fanelli, A. J. molec. Biol. 12, 375 (1965).

    Article  CAS  Google Scholar 

  4. Bunn, H. F., Forget, B., Ranney, H. M. Human Hemoglobins (Saunders, Philadelphia, 1977).

    Google Scholar 

  5. Vissers, M. C. M., Winterbourn, C. C. & Carrell, R. W. Br. J. Haemat. 53, 417–422 (1983).

    Article  CAS  Google Scholar 

  6. Weatherall, D. J. & Clegg, J. B. The Thalassemia Syndromes 3rd ed (Blackwell, Oxford, 1981).

    Google Scholar 

  7. Huisman, T. H. J. Am. J. Hemat. 14, 393–404 (1983).

    Article  CAS  Google Scholar 

  8. Tainsky, M. & Edelstein, S. J. J. molec. Biol. 75, 735–739 (1973).

    Article  CAS  Google Scholar 

  9. Valdes, R. & Ackers, G. K. Proc. natn. Acad. Sci. U.S.A. 75, 311–314 (1978).

    Article  ADS  CAS  Google Scholar 

  10. Kurtz, A., Rollema, H. S. & Bauer, C. Archs Biochem. Biophys. 210, 200–203 (1981).

    Article  CAS  Google Scholar 

  11. Kurtz, A. & Bauer, C. Biochem. biophys. Res. Commun. 84, 852–857 (1978).

    Article  CAS  Google Scholar 

  12. Valdes, R. & Ackers, G. K. J. biol. Chem. 252, 74–81 (1977).

    CAS  PubMed  Google Scholar 

  13. McDonald, M. J. & Noble, R. W. J. biol. Chem. 247, 4282–4287 (1972).

    CAS  PubMed  Google Scholar 

  14. Bucci, E. & Fronticelli, C. J. biol. Chem. 240, 551–552 (1965).

    Google Scholar 

  15. Sugita, Y. J. biol. Chem. 250, 1251–1256 (1975).

    CAS  PubMed  Google Scholar 

  16. Philo, J. S., Adams, M. L. & Schuster, T. M. J. biol. Chem. 256, 7917–7924 (1981).

    CAS  PubMed  Google Scholar 

  17. McDonald, M. J. J. biol. Chem. 256, 6487–6490 (1981).

    CAS  PubMed  Google Scholar 

  18. Turci, S. M. & McDonald, M. J. Biochem. biophys. Res. Commun. 111, 55–60 (1983).

    Article  CAS  Google Scholar 

  19. Abraham, E. C. & Huisman, T. H. J. Haemoglobin 1, 861–873 (1977).

    Article  CAS  Google Scholar 

  20. Shaeffer, J. R., Kingston, R. E., McDonald, M. J. & Bunn, H. F. Nature 276, 631–633 (1978).

    Article  ADS  CAS  Google Scholar 

  21. Shaeffer, J. R. J. biol. Chem. 255, 2322–2324 (1980).

    CAS  PubMed  Google Scholar 

  22. Righetti, P. G. & Caravaggio, T. J. Chromatog. 127, 1–28 (1976).

    Article  CAS  Google Scholar 

  23. Bunn, H. F. et al. Proc. natn. Acad. Sci. U.S.A. 79, 7527–7531 (1982).

    Article  ADS  CAS  Google Scholar 

  24. Bank, A. & O'Donnell, J. V. Nature 222, 295–296 (1969).

    Article  ADS  CAS  Google Scholar 

  25. Chalevelakis, G., Clegg, J. B. & Weatherall, D. J. Proc. natn. Acad. Sci. U.S.A. 72, 3853–3857 (1975).

    Article  ADS  CAS  Google Scholar 

  26. Hanash, S. M. & Rucknagel, D. L. Proc. natn. Acad. Sci. U.S.A. 75, 3427–3431 (1978).

    Article  ADS  CAS  Google Scholar 

  27. Testa, V. et al. J. Lab. clin. Med. 98, 352–363 (1981).

    CAS  PubMed  Google Scholar 

  28. Sancar, G. B., Cedeno, M. M. & Rieder, R. F. Blood 57, 967–971 (1981).

    CAS  PubMed  Google Scholar 

  29. Shaeffer, J. R. Blood 60, 38a (1982).

    Google Scholar 

Download references

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Authors and Affiliations

  1. Laboratory of the Howard Hughes Medical Institute, Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA

    H. Franklin Bunn & Melisenda J. McDonald

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  1. H. Franklin Bunn
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  2. Melisenda J. McDonald
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Bunn, H., McDonald, M. Electrostatic interactions in the assembly of haemoglobin. Nature 306, 498–500 (1983). https://doi.org/10.1038/306498a0

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