Uptake of Fe III influences the topographical arrangement of N-glycan(s) in human transferrin

The relative prominence of sialyl and α-mannosyl residues of apo- and metal-bound transferrin were compared. Although the presence or absence of Fe^III did not significantly affect the rate of desialylation of the glycoprotein, equilibrium dialysis with serotonin revealed substantial differences between apo- and metalbound transferrins: binding of serotonin by Fe^III-transferrin (2.3 residues/mol) exceeded that of Cu^II- or Mn^II-transferrin (each 1.3 residues/mol); in comparison apo-transferrin (0.6 residues/mol) and Fe^III-asialo-transferrin (0.5 residues/mol) bound significantly less serotonin. In the case of α-mannosyl residues, differences between certain metal-bound transferrins were observed from Sepharose-concanavalin A chromatography. Thus 20–24% of Fe^III-transferrin passed through the lectin column compared to 12–16% for Mn^II-and Cu^II-transferrins. We conclude that incorporation of metal ions, particularly Fe^III, which is known to change the tertiary structure of transferrin, alters the position(s) of the N-glycan(s) relative to the polypeptide. Such a change may govern the destiny of apo- and metal-bound transferrin in the circulation.