Ferritin: design and formation of an iron-storage molecule

Ford, Geoffrey C.; Harrison, Pauline M.; Rice, David W.; Smith, John L.; Treffry, Amyra; White, Janice L.; Yariv, J.

doi:10.1098/rstb.1984.0046

Cited by 543 publications

(228 citation statements)

References 41 publications

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“…Overexpression of the TfR1 transgene led to a decrease in endogenous TfR1 mRNA levels. This was not unexpected because the 3′ untranslated region (UTR) of the endogenous TfR1 mRNA contains five iron responsive elements (IREs), which ensures that the mRNA is degraded when intracellular iron concentrations are high 24, 25, 26. To prevent the TfR1 transgene from being regulated by this negative feedback loop, we used the previously described strategy of deleting the IREs from the 3′UTR, which enables high levels of the exogenous TfR1 mRNA to accumulate in the cells 11, 19.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the effectiveness of transferrin receptor‐1 (TfR1) as a magnetic resonance reporter gene

Pereira

Herrmann

Moss

et al. 2016

Contrast Media & Molecular

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Magnetic resonance (MR) reporter genes have the potential for tracking the biodistribution and fate of cells in vivo, thus allowing the safety, efficacy and mechanisms of action of cell‐based therapies to be comprehensively assessed. In this study, we evaluate the effectiveness of the iron importer transferrin receptor‐1 (TfR1) as an MR reporter gene in the model cell line CHO‐K1. Overexpression of the TfR1 transgene led to a reduction in the levels of endogenous TfR1 mRNA, but to a 60‐fold increase in total TfR1 protein levels. Although the mRNA levels of ferritin heavy chain‐1 (Fth1) did not change, Fth1 protein levels increased 13‐fold. The concentration of intracellular iron increased significantly, even when cells were cultured in medium that was not supplemented with iron and the amount of iron in the extracellular environment was thus at physiological levels. However, we found that, by supplementing the cell culture medium with ferric citrate, a comparable degree of iron uptake and MR contrast could be achieved in control cells that did not express the TfR1 transgene. Sufficient MR contrast to enable the cells to be detected in vivo following their administration into the midbrain of chick embryos was obtained irrespective of the reporter gene. We conclude that TfR1 is not an effective reporter and that, to track the biodistribution of cells with MR imaging in the short term, it is sufficient to simply culture cells in the presence of ferric citrate. Copyright © 2016 The Authors Contrast Media & Molecular Imaging Published by John Wiley & Sons Ltd.

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Section: Discussionmentioning

confidence: 99%

Evaluating the effectiveness of transferrin receptor‐1 (TfR1) as a magnetic resonance reporter gene

Pereira

Herrmann

Moss

et al. 2016

Contrast Media & Molecular

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“…One of the major branches of this family is the so-called mammaliantype ferritins, which have been widely studied, and are found in mammals, fish, invertebrates, and other eukaryotes [2][3][4][5][6]. The structure of horse spleen ferritin has been determined by single-crystal X-ray diffraction analysis and consists of 24 subunits of approx.…”

Section: Introductionmentioning

confidence: 99%

“…The structure of horse spleen ferritin has been determined by single-crystal X-ray diffraction analysis and consists of 24 subunits of approx. 20 000 Da arranged in 432 point symmetry to form a hollow spherical shell into which up to 4000 iron atoms can be deposited [3]. The mineral core is primarily made up of hydrated ferric oxide or ferrihydrate [7].…”

Section: Introductionmentioning

confidence: 99%

Fungal ferritins: The ferritin from mycelia of Absidia spinosa is a bacterioferritin

Carrano¹,

Böhnke²,

Matzanke³

1996

FEBS Letters

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Two distinct ferritin like iron containing proteins have been identified and isolated from the fungus Absidia spinosa; one from the spores and another from the mycelia. The mycelial protein has been purified and consists of two subunits of approx. 20 kDa. The N-terminal sequences of both subunits have been determined. The holoprotein as isolated contains approx. 750 iron atoms/molecule and exhibits a beme-like UV-Vis spectrum. Based on the beme spectrum and the high degree of sequence homology found, it has been established that the mycelial protein is a bacterioferritin. This is the first example demonstrating the presence of a bacterioferritin in a eukaryotic organism.

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“…Ferritin are oligomeric proteins of 24 identical or similar subunits related by 432 symmetry (Figure 1), each of molecular weight around 20 kDa, forming a hollow protein shell of 120 Å external diameter and 80 Å internal diameter (Ford et al 1984). The molecular weight ranges from 450 to 500 kDa, and up to 4500 iron atoms can be stored in its internal cavity in mammalian ferritins in the form of ferrihydrite micelles.…”

Section: Introductionmentioning

confidence: 99%

“…B and D helices are located on the interior of the protein shell whereas the A and C helices and the L loop are on the external surface of the molecule (Ford et al 1984).…”

Section: Introductionmentioning

confidence: 99%

EPR Studies of Recombinant Horse L-Chain Apoferritin and its Mutant (E 53,56,57,60 Q) with Haemin

2006

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Structural similarities between ferritins and bacterioferritins have been extensively demonstrated. However, there is an essential difference between these two types of ferritins: whereas bacterioferritins bind haem, in-vivo, as Fe(II)-protoporphyrin IX (this haem is located in a hydrophobic pocket along the 2-fold symmetry axes and is liganded by two axial Met 52 residues), eukaryotic ferritins are non-haem iron proteins. However, in in-vivo studies, a cofactor has been isolated from horse spleen apoferritin similar to protoporphyrin IX; in in-vitro experiments, it has been shown that horse spleen apoferritin is able to interact with haemin (Fe(III)-protoporphyrin IX). Studies of haemin incorporation into horse spleen apoferritin have been carried out, which show that the metal free porphyrin is found in a pocket similar to that which binds haem in bacterioferritins (Pre´cigoux et al. 1994 Acta Cryst D50, 739-743). A mechanism of demetallation of haemin by L-chain apoferritins was subsequently proposed (Crichton et al. 1997 Biochem 36, 15049-15054) which involved four Glu residues (E 53,56,57,60) situated at the entrance of the hydrophobic pocket and appeared to be favoured by acidic conditions. To verify this mechanism, these four Glu have been mutated to Gln in recombinant horse L-chain apoferritin. We report here the EPR spectra of recombinant horse L-chain apoferritin and its mutant with haemin in basic and acidic conditions. These studies confirm the ability of recombinant L-chain apoferritin and its mutant to incorporate and demetallate the haemin in acidic and basic conditions.

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Ferritin: design and formation of an iron-storage molecule

Cited by 543 publications

References 41 publications

Evaluating the effectiveness of transferrin receptor‐1 (TfR1) as a magnetic resonance reporter gene

Evaluating the effectiveness of transferrin receptor‐1 (TfR1) as a magnetic resonance reporter gene

Fungal ferritins: The ferritin from mycelia of Absidia spinosa is a bacterioferritin

EPR Studies of Recombinant Horse L-Chain Apoferritin and its Mutant (E 53,56,57,60 Q) with Haemin

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