[[Regulation by Fur]] and [[Why is iron important]] might be useful staring points to know why Iron storage could be needed. But it helps prevent the accumulation of insoluble Fe3+ in the cytoplasm and keeps the cell safe from Fe2+ *Pseudomonas aeruginosa* and *Escherichia coli* both have three proteins that are involved in the storage of iron; **FtnA**, **BfrB** and **Dps** (Less understood in Pa). Bacterioferritins and Dps structures are a specific sub-type of ferritins and the structures of FtnA and BfrB are pretty similar in structure however they are distinct in their amino acid sequence. # Iron storage ### Ferritins and bacterioferritin's The nanocage is assembled from 12 homodimers of BfrB or FtnA (24-mer). Structurally, the homopolymeric complexes are very similar: BfrB and FtnA are structurally conserved but sequentially divergent. Furthermore, BfrB has the unique ability to bind Haems, which FtnA does not. Each Bacterioferritin nanocage can bind up to 12 Haems in between the interface of the BfrB dimers with interactions between methionine residues. The nanocage external diameter is 120Å and has an internal diameter of 80Å and stores about 3000 Fe3+ atoms. A study was done investigating the presence of heteropolymeric complexes consisting of both BfrB and FtnA looking at the relative amounts of each type of subunit in the heterooligomer. It was observed that the ratio varies dependent on cellular O2 levels- in low O2 conditions FtnA subunits prevail; this would also result in less Haem in the complex. (Yao et al., 2022) Each subunit consists of 4 helix bundles with a ferrioxidase core that can oxidise two Fe2+ to Fe3+ , using O2 as a substrate, allowing for the storage of Fe3+. The ferrioxidase core is made of conserved residues from parts of all 4 helix bundles. In order for Fe3+ to be released from the stores, a [[ferridoxin]] is required. Electrons are transferred to Fe3+ by the [2Fe-2S] cluster in the [[Ferridoxin]] and mediated by heme, resulting in Fe2+ which can then be released when required. ![[4E6K.png|300]] PDB:4E6K Bacterioferritin and ferridoxin ### Dps DNA-binding protein from starved cells or Dps proteins are unique to prokaryotes and forms a 12-mer complex and can contain about 500 iron atoms in its 40Å cavity. As evident by its name it can also bind to DNA serving as protective mechansim during times of cell stress. it is much less conserved than its BfrB and FtnA counterparts, including variations in the key residues in the ferrioxidase core. However Dps is more conserved in its iron binding residues at this site, and is also able to bind two iron atoms- with site 1 having a higher propensity to bind iron than site 2. additionally in the oxidation of Fe2+ it prefers to use H2O2 as a substrate but can use O2 less efficiently. Curiously investigations into Dps revealed that it more stably forms a 12-mer at pH 6 and doesn't require divalent cations to assemble. However, at pH 7.5 divalent cations are required for efficient assembly into a 12-mer. Furthermore, at pH 6 the divalent cations aid in DNA binding by an unknown mechanism. ![[8W1E.png|300]] PDB: 8W1E Dps 12-Mer Pa **References** - [Rajapaksha, N., Soldano, A., Yao, H., Donnarumma, F., Kashipathy, M.M., Seibold, S., Battaile, K.P., Lovell, S. and Rivera, M. (2023). Pseudomonas aeruginosa Dps (PA0962) Functions in H2O2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity. _International Journal of Molecular Sciences_, [online] 24(5), p.4669. doi:https://doi.org/10.3390/ijms24054669.](https://pmc.ncbi.nlm.nih.gov/articles/PMC10002758/) - [Soldano, A., Yao, H., Achala N. D. Punchi Hewage, Meraz, K., Annor‐Gyamfi, J.K., Bunce, R.A., Battaile, K.P., Lovell, S. and Rivera, M. (2020). Small Molecule Inhibitors of the Bacterioferritin (BfrB)–Ferredoxin (Bfd) Complex Kill Biofilm-Embedded _Pseudomonas aeruginosa_ Cells. _ACS Infectious Diseases_, 7(1), pp.123–140. doi:https://doi.org/10.1021/acsinfecdis.0c00669.](https://pmc.ncbi.nlm.nih.gov/articles/PMC7802073/#:~:text=Our%20work%20has%20showed%20that,the%20main%20iron%20storage%20protein.&text=Bacterioferritin%2C%20which%20only%20exists%20in,cavity%20(Figure%201A).&text=We%20demonstrated%20that%20mobilization%20of,%2Dassociated%20ferredoxin%20(Bfd).&text=The%20structure%20of%20Bfd%20revealed,molecule%20(Figure%201B).&text=The%20heme%20mediates%20electron%20transfer,Fe2+%20to%20the%20cytosol.&text=The%20Bfd%20binding%20sites%20on,Kd%20of%203%20%CE%BCM.) - [Yao, H., Soldano, A., Fontenot, L., Donnarumma, F., Lovell, S., Chandler, J.R. and Rivera, M. (2022). Pseudomonas aeruginosa Bacterioferritin Is Assembled from FtnA and BfrB Subunits with the Relative Proportions Dependent on the Environmental Oxygen Availability. _Biomolecules_, [online] 12(3), p.366. doi:https://doi.org/10.3390/biom12030366.](https://pmc.ncbi.nlm.nih.gov/articles/PMC8945002/)