The iron redox and hydrolysis chemistry of the ferritins

• Published in: Biochimica et biophysica acta 2010-08, Vol.1800 (8), p.719-731
• Main Author: Bou-Abdallah, Fadi
• Format: Article
• Language: English
• Subjects: Animals; Catalytic Domain; Di-iron oxo complex; Di-iron peroxo complex; Ferritin channel; Ferritins - chemistry; Ferritins - metabolism; Ferroxidase center; H- and L-subunit; Heteropolymer; Humans; Hydrolysis; Iron - chemistry; Iron - metabolism; Iron detoxification; Iron oxidation; Kinetics; Mineral core formation; Models, Biological; Models, Molecular; Oxidation-Reduction; Protein Conformation
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2010.03.021

Ferritins are ubiquitous and well-characterized iron storage and detoxification proteins. In bacteria and plants, ferritins are homopolymers composed of H-type subunits, while in vertebrates, they typically consist of 24 similar subunits of two types, H and L. The H-subunit is responsible for the rapid oxidation of Fe(II) to Fe(III) at a dinuclear center, whereas the L-subunit appears to help iron clearance from the ferroxidase center of the H-subunit and support iron nucleation and mineralization. Despite their overall similar structures, ferritins from different origins markedly differ in their iron binding, oxidation, detoxification, and mineralization properties. This chapter provides a brief overview of the structure and function of ferritin, reviews our current knowledge of the process of iron uptake and mineral core formation, and highlights the similarities and differences of the iron oxidation and hydrolysis chemistry in a number of ferritins including those from archaea, bacteria, amphibians, and animals. Prokaryotic ferritins and ferritin-like proteins (Dps) appear to preferentially use H 2O 2 over O 2 as the iron oxidant during ferritin core formation. While the product of iron oxidation at the ferroxidase centers of these and other ferritins is labile and is retained inside the protein cavity, the iron complex in the di-iron cofactor proteins is stable and remains at the catalytic site. Differences in the identity and affinity of the ferroxidase center ligands to iron have been suggested to influence the distinct reaction pathways in ferritins and the di-iron cofactor enzymes. The ferritin 3-fold channels are shown to be flexible structures that allow the entry and exit of different ions and molecules through the protein shell. The H- and L-subunits are shown to have complementary roles in iron oxidation and mineralization, and hydrogen peroxide appears to be a by-product of oxygen reduction at the FC of most ferritins. The di-iron(III) complex at the FC of some ferritins acts as a stable cofactor during iron oxidation rather than a catalytic center where Fe(II) is oxidized at the FC followed by its translocation to the protein cavity.