Diversity of Fe 2+ entry and oxidation in ferritins

Abstract

The essential metal iron presents two major problems for life: it is potentially highly toxic due to its redox activity, and its extremely low solubility in aqueous solution in the presence of O can make it hard to acquire and store safely. Ferritins are part of nature's answer to these problems, as they store iron in a safe but accessible form in all types of cells. How they achieve this has been the subject of intense research for several decades. Here, we highlight recent progress in elucidating the routes by which Fe ions access the catalytic ferroxidase centers, and the mechanisms by which Fe is oxidized. Emerging from this is a picture of diversity, both in terms of Fe entry pathways and the roles played by the structurally distinct diiron ferroxidase centers.

Iron Oxidation and Core Formation in Recombinant Heteropolymeric Human Ferritins

“…50,51 A ferroxidase center is not a requirement for in vitro core formation because the human L-subunit homopolymer, HuLF, is also capable forming a mineral core albeit at a slower rate. 4,33,51 Heteropolymeric human ferritins, being composed of both types of subunits (i.e., H and L), are a special case. Here, we have explored two such heteropolymers, an H-rich ferritin consisting of ~20H:4L and an L-rich ferritin of ~2H:22L, representing opposite ends of the spectrum of subunit composition, and have studied the complementary functions of H- and L-subunits and compared the results with those of homopolymeric HuHF and HuLF ferritins.…”

Direct Evidence for Ferrous Ion Oxidation and Incorporation in the Absence of Oxidants by Dps from Marinobacter hydrocarbonoclasticus

“…[7,8,27] Each ferroxidase site,l ocated at dimer interfaces,i sc omposed of three conserved amino acid residues:anaspartate and aglutamate residue,f rom one monomer,a nd ah istidine residue from an adjacent monomer.S uch type of coordination sphere is compatible with the observed Mçssbauer parameters.A dditional ferrous ions could be located in uptake channels either in hexa-aquo complex form and/or interacting with other polar and negatively charged residues. [5,6] To further characterize the reaction mechanism, asample with both 57 Fe II and hydrogen peroxide with aFe II /Dps molar ratio of 96 was prepared using the same method as before and subsequently reacted, in anaerobic conditions,with additional 12 56 Fe II /Dps (thus reversing the 56 Fe/ 57 Fe order of additions). TheM çssbauer spectrum (acquired at 80 K; Supporting Information, Figure S6A) shows ad oublet species that can be fitted with two quadrupole doublets with d = 0.47 AE 0.02 mm s À1 and DE Q = 0.59 AE 0.03 and 0.99 AE 0.03 mm s À1 , respectively,t ypical of ferric iron in the mineral core.A n additional line of smaller intensity can also be observed at + 1.9 mm s À1 .T his line (which is not observed in the parallel control sample where the addition of 12 56 Fe II /Dps was omitted;S upporting Information, Figure S6B) can be assigned to the high-energy line of ad oublet species with d = 0.71 AE 0.03 mm s À1 and DE Q = 2.10 AE 0.05 mm s À1 .T he observed parameters are consistent with mixed-valence iron where an electron is delocalized between two iron atoms.…”

“…[1][2][3] From an evolutionary point of view,proteins of the ferritin superfamily share ac ommon structural theme,s elfassembling in almost spherical hollow cage-like structures made of 12 (mini-ferritins) or 24 (maxi-ferritins) polypeptide chains.P roteins of the maxi-ferritin family show octahedral symmetry and can be formed by one or two types of polypeptide chains with subunit composition dependent on organism or organ. [4,5] They can be found in prokaryotes and eukaryotes and are mainly responsible for iron oxidation and storage.A rchaeal maxi-ferritins,b acterial maxi-ferritins, bacterioferritins (which have an additional heme co-factor at the interface of each dimer), and eukaryotic maxi-ferritins are all members of this family. [1,5] Mini-ferritins are tetrahedrally symmetric,f ormed by as ingle type of polypeptide chain.…”

“…[4,5] They can be found in prokaryotes and eukaryotes and are mainly responsible for iron oxidation and storage.A rchaeal maxi-ferritins,b acterial maxi-ferritins, bacterioferritins (which have an additional heme co-factor at the interface of each dimer), and eukaryotic maxi-ferritins are all members of this family. [1,5] Mini-ferritins are tetrahedrally symmetric,f ormed by as ingle type of polypeptide chain. [6,7] Them ini-ferritin family is defined by Dps (DNAbinding protein from starved cells) and is present in prokaryotes.…”

Tyr25, Tyr58 and Trp133 ofEscherichia colibacterioferritin transfer electrons between iron in the central cavity and the ferroxidase centre

“…8 In order for either BFR or Ftn to lay down an iron-containing mineral in their central cavities, the protein takes up Fe 2+ and catalyses its oxidation to Fe 3+ by O 2 (or H 2 O 2 ). 2,3,10 Thus, oxidation of Fe 2+ is a key feature of the iron storage role of some ferritins, and it also seems to be important in dealing with oxidative stress in bacteria. Such stress occurs when the cell becomes burdened with too great a concentration of reactive oxygen species (ROS).…”