Redox Properties of Human Transferrin Bound to Its Receptor

• Published in: Biochemistry (Easton) 2004-01, Vol.43 (1), p.205-209
• Main Authors: Dhungana, Suraj, Taboy, Céline H, Zak, Olga, Larvie, Mykol, Crumbliss, Alvin L, Aisen, Philip
• Format: Article
• Language: English
• Subjects: Electron Spin Resonance Spectroscopy; Ferric Compounds - chemistry; Ferric Compounds - metabolism; Ferrous Compounds - chemistry; Ferrous Compounds - metabolism; Humans; Kinetics; Oxidation-Reduction; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Protein Binding; Receptors, Transferrin - chemistry; Receptors, Transferrin - metabolism; Receptors, Transferrin - physiology; Thermodynamics; Transferrin - chemistry; Transferrin - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi0353631

Virtually all organisms require iron, and iron-dependent cells of vertebrates (and some more ancient species) depend on the Fe3+-binding protein of the circulation, transferrin, to meet their needs. In its iron-donating cycle, transferrin is first captured by the transferrin receptor on the cell membrane, and then internalized to a proton-pumping endosome where iron is released. Iron exits the endosome to enter the cytoplasm via the ferrous iron transporter DMT1, a molecule that accepts only Fe2+, but the reduction potential of ferric iron in free transferrin at endosomal pH (∼5.6) is below −500 mV, too low for reduction by physiological agents such as the reduced pyridine nucleotides with reduction potentials of −284 mV. We now show that in its complex with the transferrin receptor, which persists throughout the transferrin-to-cell cycle of iron uptake, the potential is raised by more than 200 mV. Reductive release of iron from transferrin, which binds Fe2+ very weakly, is therefore physiologically feasible, a further indication that the transferrin receptor is more than a passive conveyor of transferrin and its iron.