Lability of iron at the dinuclear centres of ferritin studied by competition with four chelators

Treffry, Amyra; Hawkins, Chris; Williams, John M.; Guest, John R.; Harrison, Pauline M.

doi:10.1007/s007750050022

Cited by 12 publications

(11 citation statements)

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“…Moreover, the subsequent increase of the fluorescence signal ( t l l Z -450 s) must be related to factors other than iron oxidation, namely to the migration of Fe(II1) from the ferroxidase center to the nucleation sites in the internal cavity, a process that cannot be singled out by optical absorption which monitors Fe(II1) formation. This interpretation is in good agreement with the model of iron incorporation proposed on the basis of other spectroscopic experiments (Bauminger et al, 1989;Treffry et al, 1996) and of crystallographic data (Hempstead et al, 1994). It is also consistent with the fluorescence changes observed upon stepwise addition of iron (Fig.…”

Section: Discussionsupporting

confidence: 92%

Formation and movement of Fe(III) in horse spleen, H‐ and L‐recombinant ferritins. A fluorescence study

et al. 1998

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Iron oxidation and incorporation into apofemtins of different subunit composition, namely the recombinant H and L homopolymers and the natural horse spleen heteropolymer (10-15% H), have been followed by steady-state and time-resolved fluorescence. After aerobic addition of 100 Fe(I1) atoms/polymer, markedly different kinetic profiles are observed. In the rL-homopolymer a slow monotonic fluorescence quenching is observed which reflects binding, slow oxidation at the threefold apoferritin channels, and diffusion into the protein cavity. In the rH-homopolymer a fast fluorescence quenching is followed by a partial, slow recovery. The two processes have been attributed to Fe(I1) binding and oxidation at the ferroxidase centers and to Fe(II1) released into the cavity, respectively. The fluorescence kinetics of horse spleen apoferritin is dominated by the H chain contribution and resembles that of the H homopolymer. It brings out clearly that the rate of the overall process is limited by the rate at which Fe(II1) leaves the ferroxidase centers of the H chains where binding of incoming Fe(I1) and its oxidation take place. The data obtained upon stepwise addition of iron and the results of optical absorption measurements confirm this picture. The correspondence between steady-state and time-resolved data is remarkably good; this is manifest when the latter are used to calculate the change in fluorescence intensity as apparent in the steady-state measurements.

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Section: Discussionsupporting

confidence: 92%

Formation and movement of Fe(III) in horse spleen, H‐ and L‐recombinant ferritins. A fluorescence study

et al. 1998

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“…However, there are similarities between the residues at the holding sites and those proposed for the heavy chains of ferritin [23]. H-type ferritins from humans, Escherichia coli ferritin and haem-containing bacterioferritin from E. coli have been found to bind a variety of metals at a dinuclear site situated within the subunit four-helix bundle.…”

Section: Co(ii)mentioning

confidence: 93%

An X-ray structural study of human ceruloplasmin in relation to ferroxidase activity

et al. 1997

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The role of ceruloplasmin as a ferroxidase in the blood, mediating the release of iron from cells and its subsequent incorporation into serum transferrin, has long been the subject of speculation and debate. However, a recent X-ray crystal structure determination of human ceruloplasmin at a resolution of around 3.0 Å, in conjunction with studies associating mutations in the ceruloplasmin gene with systemic haemosiderosis in humans, has added considerable weight to the argument in favour of a ferroxidase role for this enzyme. Further X-ray studies have now been undertaken involving the binding of the cations Co(II), Fe(II), Fe(III), and Cu(II) to ceruloplasmin. These results give insights into a mechanism for ferroxidase activity in ceruloplasmin. The residues and sites involved in ferroxidation are similar to those proposed for the heavy chains of human ferritin. The nature of the ferroxidase activity of human ceruloplasmin is described in terms of its threedimensional molecular structure.

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“…When the iron content per ferritin protein cage is lower, the ferritin mineral resembles 2L ferrihydrite; as the iron content per cage increases, the mineral resembles 6L ferrihydrite [27, 28]. We compared free 2L and 6L ferrihydrite with 2L and 6L ferrihydrite inside ferritin cages for three reasons: (1) structurally distinct, microscale to macroscale iron (oxyhydr)oxide minerals have in the past influenced bacterial iron bioavailability [17, 29–31] and dissolution rates in the presence of siderophores [32]; (2) aggregation of free ferrihydrite [15–17] is faster with 2L ferrihydrite than with 6L ferrihydrite (unpublished observations); (3) ferritin protein cages, which control both mineral synthesis and dissolution [23, 24, 33], may be degraded in diseased tissue [34, 35], exposing the ferrihydrite core (hemosiderin). We compared effects of ferritin and free ferrihydrite on growth, and expression of selected genes, in wild-type and high-affinity siderophore-free, mutant strains.…”

Section: Introductionmentioning

confidence: 99%

Ferritin and ferrihydrite nanoparticles as iron sources for Pseudomonas aeruginosa

et al. 2013

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Metabolism of iron derived from insoluble and/ or scarce sources is essential for pathogenic and environmental microbes. The ability of Pseudomonas aeruginosa to acquire iron from exogenous ferritin was assessed; ferritin is an iron-concentrating and antioxidant protein complex composed of a catalytic protein and caged ferrihydrite nanomineral synthesized from Fe(II) and O2 or H2O2. Ferritin and free ferrihydrite supported growth of P. aeruginosa with indistinguishable kinetics and final culture densities. The P. aeruginosa PAO1 mutant (ΔpvdDΔpchEF), which is incapable of siderophore production, grew as well as the wild type when ferritin was the iron source. Such data suggest that P. aeruginosa can acquire iron by siderophore-independent mechanisms, including secretion of small-molecule reductant(s). Protease inhibitors abolished the growth of the siderophore-free strain on ferritins, with only a small effect on growth of the wild type; predictably, protease inhibitors had no effect on growth with free ferrihydrite as the iron source. Proteolytic activity was higher with the siderophore-free strain, suggesting that the role of proteases in the degradation of ferritin is particularly important for iron acquisition in the absence of siderophores. The combined results demonstrate the importance of both free ferrihydrite, a natural environmental form of iron and a model for an insoluble form of partly denatured ferritin called hemosiderin, and caged ferritin iron minerals as bacterial iron sources. Ferritin is also revealed as a growth promoter of opportunistic, pathogenic bacteria such a P. aeruginosa in diseased tissues such as the cystic fibrotic lung, where ferritin concentrations are abnormally high.

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Lability of iron at the dinuclear centres of ferritin studied by competition with four chelators

Cited by 12 publications

References 1 publication

Formation and movement of Fe(III) in horse spleen, H‐ and L‐recombinant ferritins. A fluorescence study

Formation and movement of Fe(III) in horse spleen, H‐ and L‐recombinant ferritins. A fluorescence study

An X-ray structural study of human ceruloplasmin in relation to ferroxidase activity

Ferritin and ferrihydrite nanoparticles as iron sources for Pseudomonas aeruginosa

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