(heme proteins) and photosynthesis (iron–sulfur proteins) and play important roles
in hydroxylation reactions (e.g., Stiles et al. 2009; Cojocaru et al. 2007) oxygen
sensing (Semenza 2009), and reduction, exemplified by the synthesis of deoxyribose nucleotides from ribonucleotides, central to DNA synthesis and replication.
Second, ferritins are antioxidants that consume iron and oxygen during mineralization. The two metabolic roles of ferritins are emphasized by genetic regulation with
oxidants and iron (Pham et al. 2004; Hintze and Theil 2005; Hintze et al. 2007). In
animals, both DNA and mRNA are regulated, and are selectively targeted by
oxygen or iron (Theil and Goss 2009). Iron and oxygen consumption to make
ferritin minerals is part of a feedback loop where excess iron and oxygen activate
ferritin DNA and mRNA to increase ferritin synthesis. Subsequent protein accumulation, which consumes iron and oxygen, decreases the signals and shuts down
ferritin synthesis (Theil and Goss 2009).
The protein nanocages of the ferritin superfamily are currently known to occur in
two sizes. First, 24 subunit ferritins were observed, in the middle of the twentieth
century, in many plant and animals tissues by using electron microscopy with the
density of the minerals as a reporter; later, other biophysical and molecular
biological methods were used to identify ferritin in bacteria (reviewed in [Theil
1987]). Ferritins occur in all tissues with a wide range of concentrations that reflect
environmental and developmental signals. In plants, ferritin is targeted exclusively
to cell organelles, whereas in animals, ferritins are in the cytoplasm, and in the
lysosomal and mitochondrial organelles. In bacteria, ferritin accumulations are
particularly sensitive to the culture phase, environmental iron, and oxidant concentrations; in logarithmic cultures of Escherichia coli, e.g., ferritin concentrations
are low unless extracellular stressors are added (Nandal et al. 2009). Smaller
ferritins or mini-ferritins, discovered as large proteins induced by stress, protect
bacterial DNA from damage by consuming ferrous ions and hydrogen peroxide;
accordingly they were first named DNA Protection During Stress (DPS) proteins
(Chiancone 2010). Only later, when protein crystal structures were obtained,
was the ferritin family protein cage structure discovered (Grant et al. 1998).
However, since the cages are built from only 12, 4 a-bundle subunits, with a
smaller cavity that accommodates a smaller mineral (<500 iron atoms), they
were called mini-ferritins to distinguish them from the larger, 24 subunit maxiferritins. Mini-ferritins, to date, are restricted to bacteria and archaea, contrasting
with maxi-ferritins found in bacteria, archaea, and eukaryotes.
2.2 Ferritin Distribution in Organisms of Land and Sea
Ferritins can be identified based on primary sequence in the genomes of archaea,
bacteria, and eukaryotes (Fig. 2.2a). Ferritins from organisms of each of the
kingdoms have been purified or expressed, heterologously, with variable levels of
characterization. Kinetic models and molecular pathways for the uptake of iron, the
oxidation from ferrous to ferric, and subsequent reduction and release have been
2 Maxi- and Mini-Ferritins: Minerals and Protein Nanocages
31
in hydroxylation reactions (e.g., Stiles et al. 2009; Cojocaru et al. 2007) oxygen
sensing (Semenza 2009), and reduction, exemplified by the synthesis of deoxyribose nucleotides from ribonucleotides, central to DNA synthesis and replication.
Second, ferritins are antioxidants that consume iron and oxygen during mineralization. The two metabolic roles of ferritins are emphasized by genetic regulation with
oxidants and iron (Pham et al. 2004; Hintze and Theil 2005; Hintze et al. 2007). In
animals, both DNA and mRNA are regulated, and are selectively targeted by
oxygen or iron (Theil and Goss 2009). Iron and oxygen consumption to make
ferritin minerals is part of a feedback loop where excess iron and oxygen activate
ferritin DNA and mRNA to increase ferritin synthesis. Subsequent protein accumulation, which consumes iron and oxygen, decreases the signals and shuts down
ferritin synthesis (Theil and Goss 2009).
The protein nanocages of the ferritin superfamily are currently known to occur in
two sizes. First, 24 subunit ferritins were observed, in the middle of the twentieth
century, in many plant and animals tissues by using electron microscopy with the
density of the minerals as a reporter; later, other biophysical and molecular
biological methods were used to identify ferritin in bacteria (reviewed in [Theil
1987]). Ferritins occur in all tissues with a wide range of concentrations that reflect
environmental and developmental signals. In plants, ferritin is targeted exclusively
to cell organelles, whereas in animals, ferritins are in the cytoplasm, and in the
lysosomal and mitochondrial organelles. In bacteria, ferritin accumulations are
particularly sensitive to the culture phase, environmental iron, and oxidant concentrations; in logarithmic cultures of Escherichia coli, e.g., ferritin concentrations
are low unless extracellular stressors are added (Nandal et al. 2009). Smaller
ferritins or mini-ferritins, discovered as large proteins induced by stress, protect
bacterial DNA from damage by consuming ferrous ions and hydrogen peroxide;
accordingly they were first named DNA Protection During Stress (DPS) proteins
(Chiancone 2010). Only later, when protein crystal structures were obtained,
was the ferritin family protein cage structure discovered (Grant et al. 1998).
However, since the cages are built from only 12, 4 a-bundle subunits, with a
smaller cavity that accommodates a smaller mineral (<500 iron atoms), they
were called mini-ferritins to distinguish them from the larger, 24 subunit maxiferritins. Mini-ferritins, to date, are restricted to bacteria and archaea, contrasting
with maxi-ferritins found in bacteria, archaea, and eukaryotes.
2.2 Ferritin Distribution in Organisms of Land and Sea
Ferritins can be identified based on primary sequence in the genomes of archaea,
bacteria, and eukaryotes (Fig. 2.2a). Ferritins from organisms of each of the
kingdoms have been purified or expressed, heterologously, with variable levels of
characterization. Kinetic models and molecular pathways for the uptake of iron, the
oxidation from ferrous to ferric, and subsequent reduction and release have been
2 Maxi- and Mini-Ferritins: Minerals and Protein Nanocages
31