Human ferritin

The cores of individual mammalian ferritin molecules are clearly visible by transmission electron microscopy as well defined nanoparticle crystallites encapsulated within the protein shell which can attain a size close to that of the 8 nm interior diameter of the protein shell (Massover, 1993). This is illustrated in Figure 6.13 for a sample of human ferritin. The amount of iron in the core is variable, and can range from zero to a maximum of approximately 4500 atoms (Fischbach and Anderegg, 1965) this corresponds to the capacity of the internal cavity for Fe(III) as... 

Ferritin is composed by the arrangement of 24 protein subunits, which results in a hollow shell of 8 nm inner diameter and 13 nm outer diameter (Fig. 13). Ferritin from vertebrates have two types of subunits heavy (H) and light (L). The subunit composition of human ferritins depends on the origin of the protein H2L22 for liver ferritin, H20L4 for muscle ferritin, etc. Access channels are formed by the intersection of subunits. The 8 channels located at the intersection of three subunits are hydrophilic while the 6 channels located at the intersection of 4 subunits are hydrophobic. The empty protein is called apoferritin (30). 

Fig. 17.2 Left A schematic picture of ferritin. (Mann, 1986, with permission ). Right Lattice image of a singie domain offerrihy-drite from the inorganic core of a human ferritin moiecuie. The fringes of ca. 0.27 nm correspond to the (110) piane (bar is 2 nm) (courtesy S. Mann).

Imagawa, M., Yoshitake, S., Ishikawa, E., Niitsu, Y, Urushizawa, L, Kanazawa, R., Tachibana, S., Nakazawa, N., and Ogawa, H., Development of highly sensitive sandwich enzyme immunoassay for human ferritin using affinity-purified anti-ferritin labelled with j6-D-galactosidase from Escherichia coll Clin. Chim. Acta 121, 277-289 (1982). 

Figure 16-4 The dinuclear iron center or ferroxidase center of human ferritin based on the structure of a terbium(III) derivative.73 Courtesy of Pauline Harrison.

Horse and human ferritins have considerable subunit diversity. The types indicated in the table are the heavy and light types. The number of subunits in P. laticostata ferritin has not been reported, but the number in a related chiton ferritin, that of Clavarizon hirtosa, has been shown to be two (77). 

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. 

The core of horse and human ferritin has been identified as crystalline ferrihydrite, 5Fe203 9H2O (49, 137), with some adventitious phosphate bound at the surface of the core. The proportion of phosphate to iron is very low. By contrast, the cores of bacterial ferritin are... 

Joshi and his co-workers (47,122) have also reported that soya ferritin containing 652 aluminum atoms per molecule can be prepared in vitro, and that both soya ferritin and human brain ferritin isolated from patients with Alzheimer s disease had elevated levels of aluminum compared to ferritins from other sources. However, in their study, Dedman et al. did not find any difference in the aluminum content of human ferritin isolated from the brains of control subjects and those with Alzheimer s disease. This topic merits further study, though the problems in analyzing small quantities of material, and minimizing contamination from extraneous aluminum, make accurate work difficult. 

The human cell lines HeLa and KB produce ferritins that are electro-phoretically distinct from normal human ferritins (18, 142), although they have close similarities to human ferritins in their immunological properties (18). Similar observations have been made with two strains of embryonic human skin cells and with HEP-2 carcinoma cells (17). Since these early reports the presence of new molecular forms of ferritin in neoplastic cells has been widely observed (143, 144). 

Figure 2-2 (A) nucleotide sequence and secondary structure of human ferritin IRE. The secondary structure is based on NMR spectroscopic studies. Residues 14 and 18 form a base-pair and the asterisk indicates the dynamic G U base-pair (Adapted from [30] and [32]). (B) Nucleotide sequence and predicted secondary structure of murine ALAS2 IRE. The NMR secondary structural results obtained for the ferritin IRE were adapted to the predicted secondary structure of ALAS2 IRE.

Figure 8-1 (a) The canonical IRE consensus motif, (b) Sequence and secondary structure of human ferritin H-chain IRE. 

Figure 3 The suggested coordination environments of the iron centres in ferritin ferroxidase sites for (a) bacterioferritin reduced form, 2 x Fe(II) (b) bacterioferritin oxidized form, 2 x Fe(III) (c) human ferritin (Fl-chain) both oxidized and reduced forms (d) E. coli ferritin (ecFTN) oxidized and reduced forms and...

Other sensor platforms have also been explored, such as surface plasmon resonance, field-effect transistors, other optical/spectrophotometric methods, for example, Raman spectroscopy and chemiluminescence, and electrochemical techniques. Very recently, Cai et al. have demonstrated that arrays of carbon-nanotube tips with an imprinted nonconducting polymer coating can recognize proteins below the picograms per liter level, using electrochemical impedance spectroscopy. Devices for the specific recognition of human ferritin and human papillomavirus-derived E7 protein were described (Figure 34). 

Harris ED, Stevens MD (1985) Receptors for ceruloplasmin in aortic cell membranes. In Mills CF, Bremner I, Chester JK (eds) Trace elements in animals and man. Slough, UK, Commonwealth Agricultural Bureau, pp 320-323 Hentze MW, Caughman SW, Rouault TA, Barriocanal JG, Dancis A, Harford JB, Klausner RD (1987) Identification of the iron-responsive element for the translational regulation of human ferritin mRNA. Science 238 1570-1573 Herd SM, Camakaris J, Christofferson R, Wookey P, Danks DM (1987) Uptake and efflux of copper-64 in Menkes disease and normal continuous lymphoid cell lines. Biochem J 247 341-347... 

Rouault TA, Hentze MW, Caughman SW, Harford JB, Klausner RD (1988) Binding of a cytosolic protein to the iron-responsive element of human ferritin messenger RNA. Science 241 1207-1210... 

Figure H.l. Mossbauer spectra of human ferritin and hemosiderin at a range of temperatures. (Reproduced with permission from Ref. 384.)...

Figure H.3 shows Mossbauer spectra of human ferritin and hemosiderin at 100 and 200 K, respectively, in various applied fields up to 10 T. The considered temperatures are well above the temperatures at...

Yang XK, Chen-Bairett Y, Arosio P, Chasteen ND. 1998. Reaction paths of iron oxidation and hydrolysis in horse spleen and recombinant human ferritins. Biochemistry 37 9743-9750. 

P. Englebienne, A. Van Hoonacker, and J. Valsamis, Rapid homogeneous imrrmnoassay for human ferritin... 

P- Englebienne, A. Van Hoonacker and J. Valsamis. Rapid homogeneous immunoassay for human ferritin in the cobas miia using colloidal gold as the reporter reagent. Clinical Chemistry 46 (12), 2000-2003 (2000). 

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