Ferritin core studies

The structure of ferritin cores has been studied by X-ray diffraction (47), electron diffraction (48), and high-resolution electron microscopy (49,50). The results indicate that the iron-containing cores of mammalian ferritins are crystalline with a unit cell based on a four-layer... 

As we stress in the following section, Fe + does not simply exit from the core of ferritin. Watt et al. (144) have completely reduced the core of horse ferritin and shown that it has a pH-dependent redox potential corresponding to 2H+ taken up by the core for each Fe + reduced to Fe ". In this study, anaerobic gel-filtration columns were used to separate reduced and partially reduced ferritin from contaminating small ions, and Mossbauer spectroscopy was employed to determine the extent of core reduction. Very little of the core iron was lost during the preparation, consistent with the low yields of Prussian blue formed by the addition of [FefCNle] to reduced ferritin (73, 146). Partially reduced ferritin cores have Mossbauer spectra indicative (50) of an iron... 

A particularly interesting synthetic model for the ferritin core is the iron (III) polymer obtained by Spiro, Saltman, and coworkers from bi-carbonate-hydrolyzed ferric nitrate solutions (6). The polymer has an approximate molecular weight of 150,000 and is about 70 A in diameter. Analytical studies indicate a composition Fc403(0H)4(N03)2 I.5H2O for the polymer. In physical size and shape, the Saltman-Spiro ball is remarkably similar to the ferritin core. The structure that has been sug-... 

Our electronic absorption spectral studies on the ferritin core itself are less definitive (8, 9). Because of strong tail absorption through the visible, we have been able to resolve only a 918-nm LF band. This band is diagnostic of [Fe(III)06]oct coordination, but without better spectra in the 400-700-nm region we cannot distinguish between exclusively [Fe(lII)06]oct and mixed [Fe(III)06]oct-[Fe(III)04]tet coordination structures. There is, however, no positive evidence for the presence of [Fe(III)04]tet units in the core and the analogy with the Saltman-Spiro ball leads us to prefer a model with [Fe(III)06]oct coordination. 

While research has shown that the iron oxyhydroxide cores in animal ferritins have the sole purpose of acting as iron storage sites, phosphate can also be associated with these cores and the levels depend on local conditions. In the case of bacterioferritins the native cores always seem to incorporate phosphate and there is some debate as to whether the molecules also perform the further function of phosphate storage. Interestingly, the cavity of bacterioferritins such as those from Eschirichia coli can also be used as a reaction vessel to lay down a variety of other mineral cores. Studies indicate that while details of the protein sequence and structure can vary, overall ferritin proteins can be regarded as possessing a constant set of structural motifs and it is these which are of particular relevance to coordination chemistry. 

It is important to stress that Mossbauer spectroscopy did not detect any divalent iron in all the samples measured. In a study using analytical transmission electron microscopy, the authors suggested that iron within the ferritin core in pathological SN and HP was present mainly as mixed ferric-ferrous iron oxides (magnetite-like or wiistite) and not as ferrihydrite that is the main mineral in control brain ferritin [31 ]. Mossbauer spectra of magnetite or wiistite differ from ferrihydrite spectra, but only ferrihydrite-like spectra were observed by MS in all pathological tissues. If other phases were present, they could be there only in minor quantities. 

Different Mossbauer and magnetometric studies have shown the superparamagnetism of ferritin iron cores. This property is also typical of ferro-... 

The Iron/Proteln Interface. Interactions of Iron with the protein coat of ferritin are most easily characterized In the early stages of core formation when most. If not all, of the Iron present Is In contact with the protein coat. In the complete core, bulk Iron Is Inorganic. To date, the protein coat has been little examined early In Iron core formation except In terms of effects on the Iron environment. Studies of the Iron early In core formation will be discussed later. 

Known compositional variations of ferritin iron cores only Involve phosphate, which can range from as much as 80% (21) to as little as 5% of the iron (21) in normal mammalian liver or spleen, the amount of phosphate in the ferritin iron core is ca. 12% of the iron (24). When the phosphate content is high, the distribution of phosphate is clearly throughout the core rather than on the surface. However, interior locations for phosphate are also suggested when the phosphate content is lower, by data on an Fe(III)ATP model complex (P Fe 1 4) (25) or by phosphate accessibility studies in horse spleen ferritin (P Fe = 1 8) (24). Based on model studies, other possible variations in core composition could Include H2O or sulfate (26). 

The sequence of steps in the biosynthesis of the ferritin iron core has been studied by analyzing the incorporation of Fe into ferritin during synthesis of the protein vivo. Ferritin, collected at various intervals after the induction of synthesis, was fractionated according to iron core size by sedimentation through gradients of sucrose (32). Fe appeared first in ferritin with small amounts of Fe, and later, the Fe appeared in fractions further down the gradient as the core size and the ratio... 

St. Pierre,T.G. Bell, S.H. Dickson, D.P.E. Mann, S. Webb, J. Moore, G.R. Williams, R.J.P. (1986) Mossbauer spectroscopic studies of the cores of human, limpet and bacterial ferritins. Biochim. Biophys. Acta 870 127-134... 

In crystalline oxides and hydroxides of iron (III) octahedral coordination is much more common than tetrahedral 43). Only in y-FegOs is a substantial fraction of the iron (1/3) in tetrahedral sites. The polymer isolated from nitrate solution is the first example of a ferric oxyhydroxide in which apparently all of the irons are tetrahedrally coordinated. From the oxyhydroxide core of ferritin, Harrison et al. 44) have interpreted X-ray and electron diffraction results in terms of a crystalline model involving close packed oxygen layers with iron randomly distributed among the eight tetrahedral and four octahedral sites in the unit cell. In view of the close similarity in Mdssbauer parameters between ferritin and the synthetic poljmier it would appear unlikely that the local environment of the iron could be very different in the two materials, whatever the degree of crystallinity. Further study of this question is needed. 

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