The Structure and Function of Ferritin

Abstract

A model of the structure of horse spleen apoferritin based on X-ray analysis at 6 Å (0.6nm) resolution shows the molecule as roughly spherical with a large internal cavity giving it a capacity to store up to about 4500 Fe atoms as hydrous Fe(III) oxide-phosphate. Heavy-atom complexes [e.g. (Nb6Cl12)2+, diameter 1.0 nm] located inside the molecule help us to define the dimensions of the protein shell and the size of channels passing through it, which provide a pathway for iron in and out of the molecule. Apoferritin rapidly accumulates iron, when presented with Fe(II) and an oxidant, and a mechanism for reconstitution has previously been proposed. If reconstituted ferritin is incubated with phosphate the product closely resembles native ferritin. If phosphate is added during reconstitution an altered product is obtained and the incorporated phosphate is released differently from that of native ferritin. It is concluded tentatively that within cells iron and phosphate are added separately to ferritin. Experimental evidence was obtained for the binding of limited amounts of Fe(III) from Fe(III) citrate by ferritin, but not by apoferritin. Native ferritin, fractionated with respect to iron content and reduced, gives apoferritins which differ in their ability to accumulate iron and in surface charge. Thus ‘isoferritins’ may differ functionally. Serum ferritin may be a protein with relatively low ‘affinity’ for iron.