Structure and spatial conformation of the iron-binding sites of transferrins.

Transferrins are iron-binding glycoproteins involved in iron metabolism and antibacterial defense mechanisms. Since the discovery of transferrins, many studies have attempted to characterize the iron ligands and to establish the conformation of the iron-binding sites. From chemical and spectroscopic studies, it was generally accepted that iron was hexacoordinated to Tyr and His residues, to a water molecule and to a (bi)carbonate ion, electrostatically linked to an Arg residue. On the basis of these studies, on the one hand, and on the basis of the homologies between the amino acid sequences of transferrins, on the other hand, predicted data have been provided about the number and location of the iron ligands. Recent X-ray crystallography studies of human lactotransferrin have partially confirmed the above-mentioned predicted data and have brought invaluable information about the nature of the ligands and the conformation of the iron-binding site. On the basis of the obtained results, a scheme has been proposed in which the iron is coordinated to 2 Tyr, 1 His and 1 Asp residues, to a (bi)carbonate linked to an Arg residue and probably to a water molecule. The iron-binding site is located at the interface between the two domains which constitute each lobe of the transferrins.