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O2 binding properties of the product of the central exon of β-globin gene

Abstract

The hypothesis that the exons of eukaryotic structural genes code for functional domains and that the partitioned arrangement of coding information may thus serve to mediate the rapid evolution of new and unique proteins from pre-existing exons1–3 is also supported by our recent studies which demonstrate that the product of the central exon of the human β-globin gene is a complete functional domain capable of binding haem tightly and specifically4,5. Moreover, an analysis of the structure/function changes induced by mutations in different parts of the haemoglobin molecule suggests that each of the three exon-encoded segments is primarily associated with different functions of haemoglobin (for example, haem-binding, haem–haem interaction)6. We have now extended our studies to determine whether the central fragment is sufficient for maintenance of a stable complex of ferrous haem with molecular oxygen and, if not, what are the minimal requirements for the expression of this activity. The results of our reconstitution experiments indicate that the isolated central exon peptide is unable to maintain a ferrous haem–dioxygen complex unless the side exon products and the complementary haem-containing subunit are present. A conformational change which accompanies the noncovalent association of fragments may account for the restoration of reversible oxygen binding.

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Craik, C., Buchman, S. & Beychok, S. O2 binding properties of the product of the central exon of β-globin gene. Nature 291, 87–90 (1981). https://doi.org/10.1038/291087a0

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