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

Abstract

That exons of eukaryotic structural genes code for functional domains and that partitioned arrangement of coding information may serve to mediate the rapid evolution of new and unique proteins from pre-existing exons is supported by recent studies which demonstrate that the product of the central exon of the human .beta.-globin gene is a complete functional domain capable of binding haem tightly and specifically. An analysis of the structure/function changes induced by mutation in different parts of the Hb molecule suggests that each of the 3 exon-encoded segments is primarily associated with different functions of Hb (e.g., heme binding, heme-heme interaction). Whether the central fragment is sufficient for maintenance of a stable complex of ferrous heme with molecular O2 and, if not, what the minimal requirements for expression of this activity were examined. The isolated central exon peptide seemed unable to maintain a ferrous heme dioxygen complex unless the side exon products and the complementary heme containing subunit were present. A conformational change which accompained the noncovalent association of fragments may account for the restoration of reversible O2 binding.