Ferritins: furnishing proteins with iron

Abstract

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores, consider how iron might be released from ferritins, and examine in detail how three selected ferritins oxidise Fe2+ to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins.

Inhibiting the BfrB:Bfd interaction in Pseudomonas aeruginosa causes irreversible iron accumulation in bacterioferritin and iron deficiency in the bacterial cytosol

“…8,12,40,44 In contrast to our findings with P. aeruginosa , FtnA is the main iron accumulator in E. coli , while the function of Bfr remains unknown. 35 The distinct physiological roles played by P. aeruginosa BfrB and E. coli Bfr are fascinating in the context that structural and biochemical characterization of these proteins have revealed important differences, despite very similar quaternary structures.…”

“…Although the reasons why bacteria would require two types of 24-mer iron storage proteins remain enigmatic, attempts to address the issue have led to the suggestion that the specific physiological roles played by Ftns and Bfrs are distinct in different bacteria. 40 For example, whereas FtnA is the main iron accumulator in E. coli cells, 35 the same role has been attributed to Bfr in Salmonella enterica typhimurium. 41 …”

“…In E. coli Bfr the ferroxidase centers are stable once formed and function as a catalytic site for O 2 reduction. 40,45,46 In comparison, the seemingly structurally identical ferroxidase centers in BfrB are not stable and function in a dual role of O 2 reduction and transit pore for the passage of Fe 3+ ions into the interior structural cavity. 8,12,20 Additional structural and dynamic characterization of BfrB revealed long-range dynamic communication between pores in the BfrB structure and ferroxidase centers.…”

Spectroscopic evidence for the role of a site of the di-iron catalytic center of ferritins in tuning the kinetics of Fe(ii) oxidation

“…On the other hand it is believed that in E.coli ferritin A (EcFtnA) three Fe(II) are simultaneously oxidized in sites A, B, and C. 21 On the basis of these data the diversity view has emerged claiming that the mechanism of Fe(II) oxidation and Fe(III) storage varies among ferritins. 14,15,22 In contrast our studies of the hyperthermophilic archaeal ferritin from Pyrococcus furiosus (PfFtn) and HuHF in comparison showed that in eukaryotic and microbial ferritins Fe(III) stays metastably in the ferroxidase center and is displaced by the incoming Fe(II). 4 This displacement of Fe(III) by Fe(II) was proposed to be the basis of a common mechanism of Fe(III)-storage among ferritins.…”

Regulating cellular trace metal economy in algae

“…In C. reinhardtii , as in land plants, ferritin is located in the chloroplast, and this is likely true in other algae and diatoms as well [33,34]. Given the location of ferritin in the chloroplast and the abundance of Fe in the photosynthetic complexes, a physiological role for ferritin in mediating Fe availability to those complexes during various developmental stages and stress conditions occurs both on land and in the oceans (reviewed in [35]). However, the regulation and roles of ferritin in Fe homeostasis differs.…”