Moving iron in ferritin: Leucine 154, a residue near Fe(III) during mineral buildup minimizes mineral dissolution

Abstract

Ferritins, ancient protein nanocages, reversibly synthesize hydrated ferric oxide concentrates; minerals with thousands of iron atoms grow in 8 nm cavities of the 12 nm cages of plant and animal ferritins. Cells use ferritin iron for iron-protein cofactor synthesis and as a trap for reactive iron from damaged iron-proteins. Recent ferritin structural studies show the iron entry path through iron ion channels, oxidoreductase sites and nucleation channels, a distance of ~ 5 nm from one end of the cage subunits (4 <img src='/image/spc_char/alpha.gif' border=0> -helix bundles) to the other. We now show that conserved L154, at the cavity entrance in a loop between helix 4 and a fifth short helix, slows mineral dissolution (50% mineral dissolution was >7 times faster in L154G ferritin). The effects on iron exit of leucine/glycine replacement in residue 154 at the end of iron entry path shows convergence of the iron entry and exit at L154 on the cage edge. The L154-dependent cage stabilization mechanism and the path that Fe(II) follows from the mineral surface to the ferritin protein are problems that remain unsolved in understanding the complex, eukaryotic ferritin protein cages that evolved for natural iron metabolism and are also used for imaging, nanocatalysis and nanomaterials.