Variable stoichiometry of Fe(II)‐oxidation in ferritin

Ferritin is an iron storage protein of wide distribution. The protein, apoferritin, is composed of 24 subunits arranged as a spherical shell with outside diam. 13 nm and inner cavity width -8 nm [I] . Up to 4500 Fe atoms can be stored in this space in the form of a ferric oxhydroxide microcrystalline core. It has been shown that apoferritin catalyses the oxidation of Fe(I1) to Fe(II1) [2-51 and the reconstituted ferritin so formed closely resembles native ferritin [3]. The mechanism of Fe(I1) oxidation within the ferritin molecules is controversial. It has been proposed [6] that all Fe’+ ions entering the molecule are oxidized on specific sites on the protein, and that these sites involve close pairs of Fe(I1) atoms, which bind molecular O2 with the simultaneous transfer of 2 eto give a Fe(III)O;--Fe(III) complex. Such a mechanism was rejected [3,4] in favour of a ‘crystal growth’ model. In this model Fe(I1) is bound by groups on the protein’s inner surface, chelation accelerates oxidation, and the Fe(III), which remains bound, forms nucleation centres on which further Fe atoms can be added without the obligatory involvement of oxidation sites on the protein. It is suggested that Fe(II)may be oxidized directly on the surface of the growing crystallites [3,7] . The finding in [l] of close pairs of Tb(III) near to 2-fold axes, might be taken to support the model in [6] , since these pairs may also represent Fe sites. However, such sites are not inconsistent with the model in [3], since they occur on the inner surface of the protein shell and could represent nucleation centres. Evidence has been provided [8] that in ferritin formation a single O2 molecule oxidizes 4 Fe(I1) without producing significant