Formation of protein-coated iron minerals

Abstract

The ability of iron to cycle between Fe(2+) and Fe(3+) forms has led to the evolution, in different forms, of several iron-containing protein cofactors that are essential for a wide variety of cellular processes, to the extent that virtually all cells require iron for survival and prosperity. The redox properties of iron, however, also mean that this metal is potentially highly toxic and this, coupled with the extreme insolubility of Fe(3+), presents the cell with the significant problem of how to maintain this essential metal in a safe and bioavailable form. This has been overcome through the evolution of proteins capable of reversibly storing iron in the form of a Fe(3+) mineral. For several decades the ferritins have been synonymous with the function of iron storage. Within this family are subfamilies of mammalian, plant and bacterial ferritins which are all composed of 24 subunits assembled to form an essentially spherical protein with a central cavity in which the mineral is laid down. In the past few years it has become clear that other proteins, belonging to the family of DNA-binding proteins from starved cells (the Dps family), which are oligomers of 12 subunits, and to the frataxin family, which may contain up to 48 subunits, are also able to lay down a Fe(3+) mineral core. Here we present an overview of the formation of protein-coated iron minerals, with particular emphasis on the structures of the protein coats and the mechanisms by which they promote core formation. We show on the one hand that significant mechanistic similarities exist between structurally dissimilar proteins, while on the other that relatively small structural differences between otherwise similar proteins result in quite dramatic mechanistic differences.

A New Role for Heme, Facilitating Release of Iron from the Bacterioferritin Iron Biomineral

“…The mechanism by which ferritins generate their iron mineral cargo has been the focus of much attention (3)(4)(5). Central to this process is an intrasubunit di-iron site called the ferroxidase center, which is found only in H-chain and H-chain-like subunits.…”

“…Ferritins are generally composed of 24 ␣-helical subunits that pack to form a highly symmetric dodecahedron protein coat with a hollow center in which large amounts of iron, in the form of a ferric oxy-hydroxide mineral, can be stored (3)(4)(5).…”

NMR reveals pathway for ferric mineral precursors to the central cavity of ferritin

“…A large cavity that occupies about 30% of the total protein volume at the center of the cage is the mineralization site of ferritin ferrihydrite. The importance of ferritin is illustrated by embryonic lethality of gene deletion in mammals (1) and resistance to oxidants in animals, plants, bacteria, and archea that reflects consumption of iron(II) and dioxygen or hydrogen peroxide (2)(3)(4)(5). Some classes of nanomaterials use ferritin nanocages as templates (6).…”

“…Some classes of nanomaterials use ferritin nanocages as templates (6). The protein nanocages self-assemble from fourhelix-bundle subunits into cages of two sizes: 12-subunit, hydrogen peroxide-consuming miniferritins of bacteria and archea, and 24-subunit maxiferritins of archea, bacteria, and higher organisms (3,4,7). Miniferritins may be the more primitive and are alternatively named DNA-binding proteins because some of them coat DNA.…”

A Histidine Aspartate Ionic Lock Gates the Iron Passage in Miniferritins from Mycobacterium smegmatis

“…Although these numbers are well below the 480 iron atoms per dodecamer that Dps proteins can carry in vitro, it is similar to the values observed in purified proteins of S. suis (9.9 Ϯ 1.6) and Streptococcus mutans (10.8 -27.5 iron atoms per dodecamer) Dps homologs (29,52). (52,53). Ferroxidation can happen with hydrogen peroxide or oxygen as the oxidizing agent.…”