Ferritin: a zinc detoxicant and a zinc ion donor.

Price, Daniel J.; Joshi, Jayant G.

doi:10.1073/pnas.79.10.3116

Cited by 56 publications

(29 citation statements)

References 22 publications

(21 reference statements)

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“…Ferritins have been found to be involved in the removal of zinc from the cytosol. 31,32 A similar function may be attributed to Dps proteins, but more experimental data are required to confirm this hypothesis.…”

Section: Ssdpr-mnmentioning

confidence: 60%

Structural and Thermodynamic Characterization of Metal Ion Binding in Streptococcus suis Dpr

Haikarainen

Thanassoulas

Stavros

et al. 2011

Journal of Molecular Biology

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The use of protein cages for the creation of novel inorganic nanomaterials has attracted considerable attention in recent years. Ferritins are among the most commonly used protein cages in nanoscience. Accordingly, the binding of various metals to ferritins has been studied extensively. Dps (DNA-binding protein from starved cells)-like proteins belong to the ferritin superfamily. In contrast to ferritins, Dps-like proteins form 12-mers instead of 24-mers, have a different ferroxidase center, and are able to store a smaller amount of iron atoms in a hollow cavity (up to ∼500, instead of the ∼4500 iron atoms found in ferritins). With the exception of iron, the binding of other metal cations to Dps proteins has not been studied in detail. Here, the binding of six divalent metal ions (Zn(2+), Mn(2+), Ni(2+), Co(2+), Cu(2+), and Mg(2+)) to Streptococcus suisDps-like peroxide resistance protein (SsDpr) was characterized by X-ray crystallography and isothermal titration calorimetry (ITC). All metal cations, except for Mg(2+), were found to bind to the ferroxidase center similarly to Fe(2+), with moderate affinity (binding constants between 0.1×10(5) M(-1) and 5×10(5) M(-1)). The stoichiometry of binding, as deduced by ITC data, suggested the presence of a dication ferroxidase site. No other metal binding sites were identified in the protein. The results presented here demonstrate the ability of SsDpr to bind various metals as substitutes for iron and will help in better understanding protein-metal interactions in the Dps family of proteins as potential metal nanocontainers.

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Section: Ssdpr-mnmentioning

confidence: 60%

Structural and Thermodynamic Characterization of Metal Ion Binding in Streptococcus suis Dpr

Haikarainen

Thanassoulas

Stavros

et al. 2011

Journal of Molecular Biology

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“…Dpr was also able to bind zinc ions. Although a physiological role for the zinc binding ability of Dpr is not known, detoxification of zinc by ferritin during overload has been reported (11,39). To date, ferritin-like proteins have not been reported in lactic acid bacteria, and neither bacteriofer- …”

Section: Discussionmentioning

confidence: 99%

An Iron-Binding Protein, Dpr, fromStreptococcus mutansPrevents Iron-Dependent Hydroxyl Radical Formation In Vitro

et al. 2002

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The dpr gene is an antioxidant gene which was isolated from the Streptococcus mutans chromosome by its ability to complement an alkyl hydroperoxide reductase-deficient mutant of Escherichia coli, and it was proven to play an indispensable role in oxygen tolerance in S. mutans. Here, we purified the 20-kDa dpr gene product, Dpr, from a crude extract of S. mutans as an iron-binding protein and found that Dpr formed a spherical oligomer about 9 nm in diameter. Molecular weight determinations of Dpr in solution by analytical ultracentrifugation and light-scattering analyses gave values of 223,000 to 292,000, consistent with a subunit composition of 11.5 to 15 subunits per molecule. The purified Dpr contained iron and zinc atoms and had an ability to incorporate up to 480 iron and 11.2 zinc atoms per molecule. Unlike E. coli Dps and two other members of the Dps family, Dpr was unable to bind DNA. One hundred nanomolar Dpr prevented by more than 90% the formation of hydroxyl radical generated by 10 M iron(II) salt in vitro. The data shown in this study indicate that Dpr may act as a ferritin-like iron-binding protein in S. mutans and may allow this catalase-and heme-peroxidase-deficient bacterium to grow under air by limiting the iron-catalyzed Fenton reaction.Bacteria living in air rely on defense systems that detoxify reactive oxygen species, such as superoxide, hydrogen peroxide, and hydroxyl radical, which are generated from incomplete reduction of oxygen by enzymatic and nonenzymatic means. These defense systems include (i) enzymes that scavenge reactive oxygen, such as superoxide dismutases (SOD), catalases, and peroxidases (46); (ii) DNA repair enzymes, such as exonuclease III, DNA polymerase, and RecA (46, 50); (iii) protein repair systems, such as thioredoxin and methionine sulfoxide reductase (15a); and (iv) proteins which regulate the cellular metabolism of iron to ameliorate the generation of reactive oxygen species (46,50).Lactic acid bacteria, including Streptococcus mutans, cannot synthesize heme and therefore lack catalase and cytochrome oxidases required for energy-linked oxygen metabolism. The growth of lactic acid bacteria, therefore, depends strictly on fermentation. Accordingly, the lactic acid bacteria are considered to have a preference for anaerobiosis. However, many lactic acid bacteria can grow in the presence of oxygen and even consume molecular oxygen through the action of flavoenzymes, such as NADH oxidase, pyruvate oxidase, and ␣-glycerophosphate oxidase (3,14,19,20,21,42). Several antioxidant enzymes, including manganese SOD (13, 33, 38, 41) and none-heme peroxidases, such as manganese-containing catalase (26, 27) and NADH peroxidase (40), which may function as substitutes for catalase, were identified and characterized in lactic acid bacteria. Previously, we identified two components of an NADH-dependent peroxidase (AhpC and Nox-1) from S. mutans (20,21,36). While studying an ahpC and nox-1 double-disruption mutant of S. mutans, we found that the mutant still showed the same level of pe...

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“…It is not known if this regulation requires the IRE motif. However, ferritin may function as a metal storage and transferring agent not only for iron, but also for zinc (Price and Joshi, 1982). Ferritin also can bind other metal ions such as cadmium, copper, beryllium, and aluminum (Price and Joshi, 1983;Fleming and Joshi, 1987;Theil, 1987).…”

Section: Regulation Ofx Laevis Ferritin Mrnamentioning

confidence: 98%

Molecular Cloning and Expression of Ferritin mRNA in Heavy Metal-PoisonedXenopus laevisCells

Muller

Vedel²,

Monnot³

et al. 1991

DNA and Cell Biology

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In a search for genes transcriptionally regulated by metal ions, we have isolated a Xenopus laevis ferritin cDNA clone, XL2-17, from cadmium-poisoned XL2 cells. The large size of the corresponding ferritin mRNA (1.4 kb) is due to the presence of a 629-nucleotide 5'-untranslated region. The Xenopus ferritin sequence is highly isologous with other vertebrate ferritins. In particular, there is a complete sequence identity for the iron-responsive element (IRE) located in the 5'-untranslated region in both XL2-17 and Rana catesbeiana ferritin mRNAs. The position of this IRE is unusual since it is located 489 nucleotides from the 5' end of the ferritin mRNA. Our analysis of phylogenetic relationships among ferritins indicates that all amphibian ferritins thus far sequenced would be more closely related to the mammalian H-type ferritin than to the L-type. The level of ferritin mRNA in XL2 cells rises 10- to 15-fold following exposure of cells to cadmium or copper. This increase is due to both transcriptional and translational regulation. A 10-fold increase was also found at the protein level. These results suggest that ferritin may be a primary detoxification response to heavy metals in Xenopus cells.

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Ferritin: a zinc detoxicant and a zinc ion donor.

Cited by 56 publications

References 22 publications

Structural and Thermodynamic Characterization of Metal Ion Binding in Streptococcus suis Dpr

Structural and Thermodynamic Characterization of Metal Ion Binding in Streptococcus suis Dpr

An Iron-Binding Protein, Dpr, fromStreptococcus mutansPrevents Iron-Dependent Hydroxyl Radical Formation In Vitro

Molecular Cloning and Expression of Ferritin mRNA in Heavy Metal-PoisonedXenopus laevisCells

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