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A radical view of ferritin

Two recent papers from Prof. Nick Le Brun's group provide novel insight into the mechanistic diversity of the ferritins - iron storage proteins that are Nature’s answer to the iron problem.

Iron is essential for virtually all forms of life but presents major problems due to its intrinsic toxicity and extremely low solubility/poor bioavailability such that iron is often a growth-limiting factor.  Ferritins are Nature’s answer to these problems as they are capable of storing thousands of iron atoms in the form of an inorganic ferric oxy-hydroxide mineral.  How the ferritin protein shell promotes and controls mineral formation has occupied researchers for more than six decades.  Working with a bacterioferritin from Escherichia coli, researchers in the Le Brun group, with collaborators in the School and at the University of Essex, have demonstrated that the protein functions via a transient radical mechanism involving a Tyr residue that lies within 4 Å of the protein’s catalytic centre.  This work, which is published in Angewandte Chemie Int Ed, establishes for the first time that iron mineralization in a ferritin is dependent on radical mediated electron transfer, and provides the first clear functional role for the near catalytic site Tyr residue, which is strictly conserved in all ferritins.

A second paper from the Le Brun group, with collaborators at the University of British Columbia, Vancouver, very recently published in the Journal of Biological Chemistry, provides novel insight into the ferritin from diatoms, unicellular photosynthetic eukaryotes that account for a significant proportion of CO2 fixation in the world’s oceans.  These organisms live in a marine environment that sees only periodic inputs of iron and the ferritin confers a significant growth advantage over other diatoms that don’t contain the protein.  The Le Brun group have shown that the diatom ferritin catalyses the oxidation of Fe(II) extremely rapidly at its catalytic centres, but mineralizes iron very, very slowly.  A single site-directed substitution at the catalytic centre was shown to have little effect on the rate of oxidation but to increase the rate of mineralization by an order of magnitude.  This points to a role for this ferritin as an iron buffer, enabling rapid re-utilisation of the cell’s scarce iron resources, rather than ‘simply’ promoting long term iron storage.

Read the publications here:

"Three Aromatic Residues are Required for Electron Transfer during Iron Mineralization in Bacterioferritin", Angew Chem Int Ed Engl. 2015 Oct 16.
DOI: 10.1002/anie.201507486

"A Diatom Ferritin Optimized for Iron Oxidation but not Iron Storage", J Biol Chem. 2015 Sept 22.