Ferritin nonheme iron core

There are a variety of types of ferritin nonheme iron core, ranging from the highly ordered cores of horse spleen ferritin to the amorphous cores of bacterioferritins. As noted... 

Physicochemical Characteristics of the Nonheme Iron Cores of Ferritins... 

Ferritin consists of 24 subunits, each with a molecular weight of 20,000. These form a protein shell —20 A thick, in most cases via noncovalent packing interactions, surrounding a space of —80 A diameter into which the nonheme iron core is laid down. Channels through the coat, formed by the subunit interfaces, allow iron to enter and leave the core 49, 63). These features are discussed in the article by Harrison and her co-workers in this volume. 

Some of the characteristics of the nonheme iron cores of ferritins and hacfers are given in Table II. As can be seen there is a wide variation in properties, though these do not seem to depend solely on overall core size. The mean core diameters measured by electron microscopy for human ferritin (84) and P. aeruginosa hacfer (100) were found to he 70-75 and 60-65 A, respectively, with, in both cases, a distribution of sizes between 55 and 80 or 85 A. The maximum core attainable for human or horse ferritin corresponds to 4500 atoms of Fe per molecule (49), or —33% of the mass of the fully loaded protein. The bacfer core contains less iron and thus is considerably less densely packed. 

Electron transfer reactions can be divided into inner-sphere and outer-sphere categories (131). The former involve a direct interaction between the electron donor and acceptor centers via a shared ligand, whereas in the latter type of reaction the coordination spheres remain separate. Some of the redox reactions involved in forming the nonheme iron core, and in mobilizing iron from it with small reductants, may involve inner-sphere reactions, but our concern here is to consider outer-sphere reactions of ferritins. 

Isomorphous tetragonal crystals are obtained for E. coli BFR, whether loaded or poor in nonheme iron (97), with marked intensity differences only at very low angles. Thus in BFR, as in the case of ferritin, the iron core mineral has little affect on the structure of the protein shell and is not structurally related to it. In this study the iron-loaded molecules were shown to contain ferrihydrite (47). The E. coli BFR with a wide range of estimated heme contents (0.5-0.01 per subunit) also gave isomorphous tetragonal crystals, as did a BFR-X fusion protein (98) containing a C-terminal extension of 14 residues (18 residues from the X protein attached after residue number 154 of BFR). The extensions probably lie within the shell, and, if so, about 60% of the cavity would be occupied by protein. This BFR takes up little or no nonheme iron and its heme content is also low (99). 

In contrast to ferritin, very little work has been done on the reconstitution of BFR cores, other than the experiments mentioned above that showed that, in the absence of phosphate, crystalline ferrihydrite formed inside the protein shell. The intermediate stages in this process are unknown, but the sigmoid iron uptake behavior (25) suggests there could be a similar succession of events oxidation and nucleation on the protein shell followed by direct oxidation on the core. The influence of the heme, if any, on BFR iron core formation also awaits investigation. As mentioned above, the presence of the iron core influences the heme redox potential, but it is not known whether the presence of heme influences the redox potential of the nonheme iron. 

Hemosiderin, a mammalian non-heme iron storage protein with a similar function to ferritin. It contains iron oxyhy-droxide cores similar to those of ferritin, and it has been reported that these cores are present as large, dense, membrane-bound aggregates in vivo. It is assumed that hemosiderin is produced by lysosomal degradation of ferritin or possibly of ferritin polymers. Hemosiderin is deposited in the liver and spleen, especially in diseases such as pernicious anemia or hemochromatosis. The deposits are yellow to brown-red pigments. The iron content of hemosiderin is about 37%. Nonheme iron is also abundantly present in the brain in different forms. In the so-called high-molecular-weight complexes, iron is bound to hemosiderin and ferritin. The total amount of iron may differ in health and disease [F. A. Fischbach et al, J. Ultrastruct. Res. 1971, 37, 495 M. P. Weir, T. J. Peters, Biochem.J. 1984, 223, 31]. 

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