Ferritin

Abstract The ferritin superfamily of protein nanocages oxidizes ferrous ions to form hydrated ferric oxide nanominerals consisting of thousands of iron and oxygen atoms, in a central, internal cavity; varying amounts of phosphate are incorporated. Maxi‐ferritins, found in all eukaryotes and many bacteria and Archea, have diameters of 10–12 nm, constructed from 24 self‐assembling polypeptide subunits (four‐α‐helix bundles) with cavities of ∼8 nm, while mini‐ferritins in bacteria assemble from 12 subunits, are ∼8 nm in diameter, and have cavities of ∼5 nm. Ferritins function in concentrating iron for protein co‐factor synthesis (heme, FeS, etc.), recovering iron during senescence, and trapping excess iron and oxygen; mini‐ferritins, also called Dps proteins, protect bacterial DNA from chemical/physical damage during stress, in some cases binding the DNA in bacterial “chromatin” structures. There are three types of Fe–protein interaction sites in the nanocages, although when mineralized, most of the iron atoms are in the inorganic phase: 1 – catalytic sites, related by simple DNA coding changes to di‐iron oxygenase co‐factors, that couple two ferrous with oxygen atoms into diferric peroxo and ferric oxy/hydroxo mineral precursors; 2 – nucleation sites on the cavity surface that initiate mineral formation; 3 – gated pores at triple subunit junctions, that control access of reductants and chelators to recover the mineral. Genetic regulation of ferritin synthesis is unusually complex, depending both on DNA, and, in animals, on mRNA structures that link ferritin to both antioxidant response proteins (DNA regulation) and iron trafficking proteins (mRNA regulation). The lethality of ferritin gene deletion in animals and the recent demonstration that humans absorb ferritin iron from seeds such as soybeans, illustrate the key role played by ferritins in the normal physiology of iron and oxygen. Exploring ferritin interactions with external cellular components that deliver/remove substrates/products, intra‐cage translocation of oxidation products/mineral precursors and reductants, and the potential use of the protein nanocage in materials or pharmacology are directions for the future.