Transferrin structure

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... 

All transferrins characterized so far consist of a single polypeptide chain of 670-700 amino acid residues. The lactoferrin and serum transferrin structure analyses show that the folding (polypeptide chain conformation) is the same in both proteins and, given their sequence homology, can be assumed to hold for all proteins of the transferrin family. 

A potentially confusing aspect of transferrin structure and function is that, prior to determination of the lactoferrin and transferrin structures, the N- and C-terminal halves of each molecule were often referred to as N- and C-domains. Given the clear subdivisions apparent in Fig. 4, however, the commonly accepted definition of protein domains (separately folded units see Ref. 83), and the functional importance of these units, it seems preferable to think of the transferrins as proteins comprising two lobes, but four domains. 

A remarkable feature of transferrin structure, discovered when the human lactoferrin structure was determined (67, 85), is the striking similarity with a group of bacterial binding proteins. These proteins, the bacterial periplasmic binding proteins, bind and transport certain small molecules, such as sugars, amino acids and oxyanions, through the periplasmic space before delivering them via specific receptors in the bacterial cell wall (111). They thus share with transferrins the... 

Most of the divalent transition metal ions bind only weakly to transferrins, the binding constants for Fe2+, Ni2+, and Zn2+ being approximately 103, 104, and 105, respectively (Table VII). Cu2+ may be an exception. Although no binding constants have been determined for any of its complexes with transferrins, and metal displacement studies indicate that it binds less strongly than Al3+ (144) and Mn3+ (154), it does form a very stable complex and has been used more than any other metal ion (apart from Fe3+) for physicochemical studies on transferrins. With its d9 electron configuration, Cu2+ has, like V02+, provided an excellent and much-used EPR probe of transferrin structure. It was the EPR spectra of Cu2+-transferrin (91), -ovotransferrin (157), and -lactoferrin (92) complexes that provided the most compelling evidence... 

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