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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Perutz, M. F. Nature 228, 726–733 (1970).
Benesch, R. & Benesch, R. E. Science 185, 905–908 (1974).
Antonini, E., Bucci, E., Fronticelli, C., Wyman, J. & Rossi-Fanelli, A. J. molec. Biol. 12, 375 (1965).
Bunn, H. F., Forget, B., Ranney, H. M. Human Hemoglobins (Saunders, Philadelphia, 1977).
Vissers, M. C. M., Winterbourn, C. C. & Carrell, R. W. Br. J. Haemat. 53, 417–422 (1983).
Weatherall, D. J. & Clegg, J. B. The Thalassemia Syndromes 3rd ed (Blackwell, Oxford, 1981).
Huisman, T. H. J. Am. J. Hemat. 14, 393–404 (1983).
Tainsky, M. & Edelstein, S. J. J. molec. Biol. 75, 735–739 (1973).
Valdes, R. & Ackers, G. K. Proc. natn. Acad. Sci. U.S.A. 75, 311–314 (1978).
Kurtz, A., Rollema, H. S. & Bauer, C. Archs Biochem. Biophys. 210, 200–203 (1981).
Kurtz, A. & Bauer, C. Biochem. biophys. Res. Commun. 84, 852–857 (1978).
Valdes, R. & Ackers, G. K. J. biol. Chem. 252, 74–81 (1977).
McDonald, M. J. & Noble, R. W. J. biol. Chem. 247, 4282–4287 (1972).
Bucci, E. & Fronticelli, C. J. biol. Chem. 240, 551–552 (1965).
Sugita, Y. J. biol. Chem. 250, 1251–1256 (1975).
Philo, J. S., Adams, M. L. & Schuster, T. M. J. biol. Chem. 256, 7917–7924 (1981).
McDonald, M. J. J. biol. Chem. 256, 6487–6490 (1981).
Turci, S. M. & McDonald, M. J. Biochem. biophys. Res. Commun. 111, 55–60 (1983).
Abraham, E. C. & Huisman, T. H. J. Haemoglobin 1, 861–873 (1977).
Shaeffer, J. R., Kingston, R. E., McDonald, M. J. & Bunn, H. F. Nature 276, 631–633 (1978).
Shaeffer, J. R. J. biol. Chem. 255, 2322–2324 (1980).
Righetti, P. G. & Caravaggio, T. J. Chromatog. 127, 1–28 (1976).
Bunn, H. F. et al. Proc. natn. Acad. Sci. U.S.A. 79, 7527–7531 (1982).
Bank, A. & O'Donnell, J. V. Nature 222, 295–296 (1969).
Chalevelakis, G., Clegg, J. B. & Weatherall, D. J. Proc. natn. Acad. Sci. U.S.A. 72, 3853–3857 (1975).
Hanash, S. M. & Rucknagel, D. L. Proc. natn. Acad. Sci. U.S.A. 75, 3427–3431 (1978).
Testa, V. et al. J. Lab. clin. Med. 98, 352–363 (1981).
Sancar, G. B., Cedeno, M. M. & Rieder, R. F. Blood 57, 967–971 (1981).
Shaeffer, J. R. Blood 60, 38a (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bunn, H., McDonald, M. Electrostatic interactions in the assembly of haemoglobin. Nature 306, 498–500 (1983). https://doi.org/10.1038/306498a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/306498a0
This article is cited by
-
The hemoglobin Gly16β1Asp polymorphism in turbot (Scophthalmus maximus) is differentially distributed across European populations
Fish Physiology and Biochemistry (2020)
-
EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies
European Journal of Human Genetics (2015)
-
Changes in alpha-globin gene expression in mice of two alpha-globin haplotypes during development
Biochemical Genetics (1990)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.