Iron and proteins for iron storage and detoxification

Abstract

Iron is required by most organisms, but is potentially toxic due to the low solubility of the stable oxidation state, Fe(III), and to the tendency to potentiate the production of reactive oxygen species, ROS. The reactivity of iron is counteracted by bacteria with the same strategies employed by the host, namely by sequestering the metal into ferritin, the ubiquitous iron storage protein. Ferritins are highly conserved, hollow spheres constructed from 24 subunits that are endowed with ferroxidase activity and can harbour up to 4500 iron atoms as oxy-hydroxide micelles. The release of the metal upon reduction can alter the microorganism-host iron balance and hence permit bacteria to overcome iron limitation. In bacteria, the relevance of the Dps (DNA-binding proteins from starved cells) family in iron storage-detoxification has been recognized recently. The seminal studies on the protein from Listeria innocua demonstrated that Dps proteins have ferritin-like activity and most importantly have the capacity to attenuate the production of ROS. This latter function allows bacterial pathogens that lack catalase, e.g. Porphyromonas gingivalis, to survive in an aerobic environment and resist to peroxide stress.

Characterization of a Mycobacterium tuberculosis Nanocompartment and Its Potential Cargo Proteins

“…These observations suggest that Enc proteins compartmentalize DyP or ferritin-like proteins via their C-terminal tails. Notably, both DyPs and ferritin proteins possess antioxidant properties (7,8).…”

Paired Bacillus anthracis Dps (Mini-ferritin) Have Different Reactivities with Peroxide

“…The proteins are stable nanocages with large (5-nm diameter) central cavities (2,3) and have been observed in vivo as part of biocrystalline complexes with DNA (e.g. see Ref.…”

“…4). Protection of DNA from damage by free radicals, the common property of Dps proteins, is accomplished by converting oxidants and iron released during stress to benign, hydrated, ferric oxide minerals inside the Dps protein cage (2,3). Because only some Dps protein dodecamers bind DNA but all protect DNA from hydroxyl radical damage in vitro, the mechanisms of Dps protein protection of DNA from oxidant damage and other stresses such as nucleases, radiation, and heat are subjects of active study (e.g.…”

“…Refs. [2][3][4][5][6][7][8][9]. When DNA-Dps interactions occur, N-or C-terminal protein extensions that protrude from the protein nanocages are thought to be involved (10,11).…”

“…Then, by mechanisms unknown, the mineral precursors move through the protein cage to the cavity and are concentrated by clustered carboxylates on the inner surface of the protein cavity and, later, at the mineral surface; inorganic hydrolysis and polymerization in the ferritin cavity form the hydrated ferric oxide minerals. Bacterial Dps proteins are miniferritins with 12 subunits (2,3,25) that contrast with the 24 in eukaryotic and bacterial maxi-ferritins. The location of the catalytic site in the protein nanocage is also different as are the active site ligands and the oxidant substrate (2, 3, 22, 26 -28).…”