The Ultrastructure of Ferritin Macromolecules. The Lattice Structure of the Core Crystallites

Abstract

The ultrastructure of the crystalline ferric mineral that forms the central core of ferritin macromolecules has been examined by means of ultrahigh resolution electron microscopy at 100 kV. Very high magnification dark-field images reveal the presence of either a single large crystal or several smaller crystallites within many of the cores. When the highly crystalline core contents are suitably oriented to transmit their Bragg reflections through the objective aperture, regular fringes separated by 2-9.5 A have been visualized. The geometrical relations of lattice fringes and of periodically organized point details in these individual crystallites largely confirm the structural model proposed by Towe and Bradley (1967). The highly variable occupancy of ferric ions in certain planes of the lattice suggests that 20-33% of the iron content of fully saturated ferritin should undergo more rapid physiological release than does the remainder, and that iron uptake will have kinetics that depend upon more than only the maximal rate of crystallization.The variable iron content of the iron storage protein, ferritin, is present in a ferric mineral located within the central cavity of its apoprotein complex, apoferritin (5, 6). X-ray and electron diffraction of ferritin (9, 10, 23) has elicited polycrystalline ring patterns, thus indicating that some of the mineral forming the core is organized into the crystalline state. Diffraction patterns from ferritin cores do not correspond to the crystal structures of the well-known iron oxides in the natural world (9). Two models, based upon the diffraction data, have been proposed for the lattice structure of ferritin core crystallites. Harrison et al. (10) have concluded that these have a hexagonal unit cell with a = 2.94 A and c = 9.40 A. The best agreement of their postulated atomic positions with the actual diffraction patterns was achieved by proposing that the iron atoms are equally and randomly distributed among all of the available sites; both tetrahedral and octahedral coordination of the iron atoms with the oxygen groups was postulated. Towe and Bradley (23) have concluded that the ferritin core crystallites have a hexagonal unit cell with a = 5.08 A and c = 9.4 A. Their model proposes that occupancy by the iron atoms is optional in one of every four layers between the close-packed oxygen groups; in this model, only octahedral coordination was postulated. In addition to these two studies, Brady et al. (1) (Fig. 3). Spatial frequencies corresponding to real lattice periodicities of around 1-5 A were transmitted to the image plane (Fig. 3); the maximum arc of the diffraction rings being transmitted was near 800. The 3847

New Data and a Revised Structural Model for Ferrihydrite

“…Towe and Bradley (1967) showed spherical aggregates formed by precipitation from ferric chloride and iron micelles within the ferritin macromolecule, both about 30-50 in diameter. Massover and Cowley (1973) similarly showed 50-~ spheres from horse-spleen ferritin. Natural ferrihydrites were also shown to be aggregates of 30-50-~ spheres (Schwertmann and Fischer, 1973;Henmi et al, 1980;Carlson and Schwertmann, 1981).…”

“…Russell (1979) has since shown that about half the hydrogen is present as OH; he suggested a formula Fe203 9 2FeO(OH).2.5H20. Massover and Cowley (1973) found TEM evidence for 9-/k lattice fringes crossed by 4.4-~ fringes in the cores of ferritin molecules, and regarded this as confirmation of the Towe and Bradley structure.…”

“…Bright field images were obtained at a nominal magnification of 810,000 using an objective aperture which included diffracted beams out to 1.4/~. Following the technique described by Massover and Cowley (1973), dark-field images were recorded using an axial aperture equivalent to 2.5 ~ radius, with the direct beam tilted so as to be just excluded. In bright field, oriented crystals were selected by their greater contrast; dark field conditions clearly showed a 9-~ (001) repeat, allowing identification of crystals oriented with their Z-axis perpendicular to the electron beam.…”

Evaluation of the Debye temperature for iron cores in human liver ferritin and its pharmaceutical analogue, Ferrum Lek, using Mössbauer spectroscopy

“…These medicaments are often regarded as pharmaceutical analogues or model compounds of ferritin. The main differences between ferritin and its analogues are in the form of the iron core which is hexagonal ferrihydrite in ferritin and tetragonal β-FeOOH in the majority of analogues such as iron-dextran [5,6] as well as in the shell.…”

Variation of superparamagnetic properties with iron loading in mammalian ferritin

“…A variety of physical techniques including X-ray and electron diffraction [6,7], high resolution transmission electron microscopy [8,9], EXAFS [10], EPR [11], NMR relaxometry [12,13], magnetic measurements [14][15][16][17], and M/Sssbauer spectroscopy [10, 14,[18][19][20][21][22][23][24][25][26] have been used to study the properties of the ferric oxy-hydroxide core particles of ferritin. The particles consist of the quasicrystalline, ferric-hydrous-oxide mineral, ferrihydrite.…”