Is His54 a gating residue for the ferritin ferroxidase site?

Bernacchioni, Caterina; Ciambellotti, Silvia; Theil, Elizabeth C.; Turano, Paola

doi:10.1016/j.bbapap.2015.02.011

Cited by 17 publications

(19 citation statements)

References 31 publications

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“…The route of iron transit has been elucidated for recombinantly expressed homopolymers of human H and frog M ferritin, largely due to the work of the groups of Theil, Turano and Mangani. [5][6][7][8][9][10] The peptide sequences of the ferritins of higher eukaryotes are highly conserved with respect to residues located close to the 3-fold channel ( Fig. S1 †), and both crystallographic data and disruption of this channel by site directed mutagenesis demonstrate that this is the route of iron entry into these proteins.…”

Section: Introductionmentioning

confidence: 99%

Routes of iron entry into, and exit from, the catalytic ferroxidase sites of the prokaryotic ferritin SynFtn

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Routes of iron entry into, and exit from, the catalytic ferroxidase sites of the prokaryotic ferritin SynFtn

et al. 2020

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“…In order to investigate the correlation between the binding abilities of different FAs and the kinetics of mineralization, commercial apo HoSF was first demineralized and then incubated with or without lipids. The kinetics of biomineral formation was followed by UV‐absorption through the change in absorbance at 350 nm, in order to monitor the formation of the diferric oxo/hydroxo species ([Fe 3+ O] x ) during oxidative deposition of iron in the apo‐ and lipid‐bound ferritin forms. A high loading of Fe 2+ (480 equivalents of Fe 2+ per HoSF cage) was employed to favor the nucleation and growth of the incipient core, namely to ensure that the mineralization reaction occurred to an appreciable extent .…”

Section: Resultsmentioning

confidence: 99%

Unsaturated Long‐Chain Fatty Acids Are Preferred Ferritin Ligands That Enhance Iron Biomineralization

Zanzoni

Pagano

D’Onofrio

et al. 2017

Chemistry A European J

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Ferritin is a ubiquitous nanocage protein, which can accommodate up to thousands of iron atoms inside its cavity. Aside from its iron storage function, a new role as a fatty acid binder has been proposed for this protein. The interaction of apo horse spleen ferritin (HoSF) with a variety of lipids has been here investigated through NMR spectroscopic ligand-based experiments, to provide new insights into the mechanism of ferritin-lipid interactions, and the link with iron mineralization. 1D H, diffusion (DOSY) and saturation-transfer difference (STD) NMR experiments provided evidence for a stronger interaction of ferritin with unsaturated fatty acids compared to saturated fatty acids, detergents, and bile acids. Mineralization assays showed that oleate c aused the most efficient increase in the initial rate of iron oxidation, and the highest formation of ferric species in HoSF. The comprehension of the factors inducing a faster biomineralization is an issue of the utmost importance, given the association of ferritin levels with metabolic syndromes, such as insulin resistance and diabetes, characterized by fatty acid concentration dysregulation. The human ferritin H-chain homopolymer (HuHF), featuring ferroxidase activity, was also tested for its fatty acid binding capabilities. Assays show that oleate can bind with high affinity to HuHF, without altering the reaction rates at the ferroxidase site.

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“…3(c). Interestingly, it has been previously postulated 8 that site B may be accessible through the four-fold channel which has been proven a possibility through mutation studies 40,41 . The activation of the four-fold channel in bullfrog ferritin enhanced the ferroxidase activity five-fold.…”

Section: Figurementioning

confidence: 99%

Iron redox pathway revealed in ferritin via electron transfer analysis

Chen

Meulenaere

Deheyn

et al. 2020

Sci Rep

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ferritin protein is involved in biological tissues in the storage and management of iron -an essential micro-nutrient in the majority of living systems. While there are extensive studies on iron-loaded ferritin, its functionality in iron delivery is not completely clear. Here, for the first time, differential pulse voltammetry (DpV) has been successfully adapted to address the challenge of resolving a cascade of fast and co-occurring redox steps in enzymatic systems such as ferritin. Using DpV, comparative analysis of ferritins from two evolutionary-distant organisms has allowed us to propose a stepwise resolution for the complex mix of concurrent redox steps that is inherent to ferritins and to fine-tune the structure-function relationship of each redox step. indeed, the cyclic conversion between fe 3+ and fe 2+ as well as the different oxidative steps of the various ferroxidase centers already known in ferritins were successfully discriminated, bringing new evidence that both the 3-fold and 4-fold channels can be functional in ferritin.Ferritin is an ubiquitous protein 1,2 involved in the storage and management of iron -an essential micro-nutrient for almost all living systems. The protein occurs in abundance in the cytosol and mitochondria, where it helps maintaining the performance of critical biochemical reactions 3-6 and balance oxidative stress processes 7 . Ferritin is therefore mainly internal in most systems, but can sometimes be a secreted enzyme 7 , and can thus be used to manage balance of iron both intra-and extracellularly, which can protect from deleterious excess of iron uptake, but also from viral and bacterial infections. Ferritin is known to take up iron (as Fe 2+ ) and store it in stable unreactive Fe 3+ -oxide/hydroxide form (primarily ferrihydrite). It is believed to deliver Fe back in a functional Fe 2+ form, where and when needed for biological processes 8 . In spite of many biochemical studies on performance of loaded ferritin, some parts of the molecular mechanisms of iron uptake, e.g., associated with oxidation steps, and most of the iron release and delivery, e.g., associated with reduction steps), remain largely unclear and speculative [8][9][10][11] .Structurally, ferritin is a biomacropolymeric enzyme constituted of 24 subunits (Fig. 1a,b) forming a hollow structure -often referred to as a cage that can be loaded 12 with Fe. The cage has an octahedral (432) symmetry where the 4-fold and 3-fold axes of symmetry are the place where 4 and 3 subunits meet together to respectively delineate six four-fold channels and eight three-fold channels. These channels have a small diameter (ranging from ~0.2 nm to ~0.5 nm) that varies along the 3 -4 nm length of the channels. To date both the 3-fold and 4-fold channels have been considered for the Fe 2+ ion entry into the core of the cage, but proof of natural activity 8,11,13 has been delivered only for the 3-fold channels. There are three types of ferritin subunits: Light (L), a Middle (M) and a Heavy (H) subunit, in increasing order of molecul...

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Is His54 a gating residue for the ferritin ferroxidase site?

Cited by 17 publications

References 31 publications

Routes of iron entry into, and exit from, the catalytic ferroxidase sites of the prokaryotic ferritin SynFtn

Routes of iron entry into, and exit from, the catalytic ferroxidase sites of the prokaryotic ferritin SynFtn

Unsaturated Long‐Chain Fatty Acids Are Preferred Ferritin Ligands That Enhance Iron Biomineralization

Iron redox pathway revealed in ferritin via electron transfer analysis

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