The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
Transferrins are iron-binding blood plasma glycoproteins that regulate the level of free iron in biological fluids. Vertebrate transferrins are made of a single polypeptide chain with a molecular weight of about 80 kDa. The polypeptide is folded into two homologous lobes (the N-lobe and C-lobe), and each lobe is further subdivided into two similar alpha helices and beta sheets domains separated by a deep cleft that forms the binding site for ferric iron. Thus, the transferrin protein contains two homologous metal-binding sites with high affinities for ferric iron. The modern transferrin proteins are thought to be evolved from an ancestral gene coding for a protein of 40 kDa containing a single binding site by means of a gene duplication event. Vertebrate transferrins are found in a variety of bodily fluids, including serum transferrins, ovotransferrins, lactoferrins, and melanotransferrins. Transferrin-like proteins are also found in the circulatory fluid of certain invertebrates. The transferrins have the same structural fold as the type 2 periplasmic-binding proteins, many of which are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor.
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