Insect transferrin

All proteins consist of a peptide chain of 680-700 amino acid residues which can be divided into two homologous halves. The insect transferrin isolated from hemolymph of Sarcophaga peregrina fly is distinct since its molecular mass is 65 kDa only and, unlike the other transferrins, the similarity between its N-terminal and C-terminal halves is only 19% [72]. 

Transferrin iron uptake via receptor-mediated endocytosis has clearly appeared fairly late in evolution, when we consider that the bilobal iron-binding protein is found only as far back as insects . As we have seen in the preceding chapters, iron-uptake mechanisms involving the synthesis of more or less specific siderophores have evolved together with strategies implying the solubilization of insoluble ferric iron by the combined effects of pH and reduction, and even the development of receptor proteins capable of taking up transferrin-, lactoferrin- or haem-bound iron from specific hosts. 

Of fundamental significance to understanding transferrin structure and function is the two-fold internal amino acid sequence repeat. In each protein, the N-terminal half of the polypeptide is homologous with the C-terminal half, with the level of identity between the two halves ranging from 26-28% in the insect proteins to —40% in higher transferrins and as high as 46% in melanotransferrin. This repeat is expressed... 

The four metal-binding amino acid residues (2 Tyr, 1 Asp, 1 His) are present in both N- and C-sites of all transferrins so far sequenced, apart from melanotransferrin and the insect proteins (Table III). The same is true of the anion-binding Arg and Thr residues, and the residues at the N-terminus of the anion-binding helix are also strongly conserved. Superposition of the 81 common atoms of these residues, plus metal and anion, shows that their rms deviation in the N- and C-sites of diferric human lactoferrin is only 0.3 A. This close structural similarity is reflected in their spectroscopic properties. Where these have been compared, with the physiological Fe3+ and C032- ions bound, they are so similar as to be virtually identical (107, 56, 199). Nevertheless, there are a number of factors that can potentially lead to inequivalence in properties ... 

In the meantime, in 1947, Laurell and Ingelman[17] had independently purified the red protein from pig plasma and in the same year proposed the name transferrin which has since been adopted as the generic name of the proteins of this family serotransferrin (instead of siderophilin) present in blood and some external secretions, ovotransferrin (instead of conalbumin) in avian egg-white, lactotransferrin (also called lactoferrin) from milk, external secretions and leukocytes and melanotransferrin (instead of p97) in melanocyte and normal cell plasma membrane. A dozen mammalian and some frog, fish and insect serotransferrins were later isolated and characterized. 

Morabito, M.A., Llewellyn, L.E., Moczydlowski, E.G., 1995. Expression of saxiphilin in insect cells and localization of the saxitoxin-binding site to the C-terminal domain homologous to the C-lobe of transferrin. Biochemistry, 34 13027-13033. 

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