Apoferritin structure

Toussaint, L., Bertrand, L., Hue, L., Crichton, R.R. and Declercq, J.-P. (2006) High-resolution X-ray structures of human apoferritin H-chain mutants correlated with their activity and metal-binding sites, J. Mol. Biol., 365, 440-452. 

In order to deal with a system whose structural characteristics were unaltered by the loading with Gd(III) chelates, we choose Apoferritin because it allows the Imaging Probes to be entrapped inside its inner cavity (60). The exterior of such Gd(III)-loaded Apoferritin is exactly the same as in the parent Ferritin and then, once administered intravenously, it is quickly cleared-up by the proper receptors on hepatocytes (172). The process of loading Apoferritin with [GdHPD03A(H20)] consists first of the dissociation of the protein into subunits at pH 2, followed by its reforming at pH 7, thereby trapping the solution components (e.g., [GdHPD03A(H20)])... 

Figure 3. Comparison of the rate of oxidation of Fe(II) when mixed with apoferritin coats (480 Fe/molecule) in 0.15 M Hepes Na, pH 7.0, using absorbance at 420 nm ( a—s— ), availability to react with -phenanthroline ( o—o—o ), change in the x-ray absorption near edge structure (XANES) ( — — ). All three types of measurements were made under the same experimental conditions, including the sample holder. (Data are taken from Ref.

Since the (Fen05(0H)6> unit is stable, it has been speculated(8b,17b) that it might also be present in the ferritin core. Since the majority of phosphate in ferritin is adventitious, surface bound and the metallic core can be reconstituted in the absence of phosphate groups with no change in the X-ray powder diffraction pattem(l), replacement of bridging phosphate by bridging carboxylate groups should not influence the three dimensional structure of the core. Calculations show that -409 Fell nnits could fill the apoferritin inner cavity. Further details can be found in reference 17. 

Harrison, P.M. (1983) The spatial structure of horse spleen apoferritin. In Theil, E.C. Eichhom, G.L. Marzilli, L.G. (eds.) Advances in inorganic biochemistry. Vol. 5, Elsevier Amsterdam, 39-61... 

Antitumor drugs cisplatin as, history, 37 175-179 platinum compounds future studies, 37 206-208 resistance to, 37 192-193 second-generation, 37 178 Antiviral agents, 36 37-38 AOR, see Aldehyde oxidoreductase Aphanothece sacrum, ferredoxins, amino acid sequence, 38 225-227 Apo-calcylin, 46 455 Apo-caldodulin, 46 449-450 Apoenzyme, 22 424 Apoferritin biosynthesis, 36 457 cystalline iron core, 36 423 Fe(III)distribution, 36 458-459 Fe(II) sequestration, 36 463-464 ferroxidase centers, 36 457-458 iron core reconstruction in shell, 36 457 mineralization, 36 25 Mdssbauer spectra, 36 459-460 optical absorbance spectra, 36 418-419 subunit conformation and quaternary structure, 36 470-471... 

Finally, Ebalunode et al. reported a structure-based shape pharmacophore modeling for the discovery of novel anesthetic compounds (88). The 3D structure of apoferritin, a surrogate target for GABAa, was used as the basis for the development of several shape pharmacophore models. They demonstrated that... 

Figure 16-3 Structure of the protein shell of ferritin (apoferritin). (A) Ribbon drawing of the 163-residue monomer. From Crichton.62 (B) Stereo drawing of a hexamer composed of three dimers. (C) A tetrad of four subunits drawn as a space-filling diagram and viewed down the four-fold axis from the exterior of the molecule. (D) A half molecule composed of 12 subunits inscribed within a truncated rhombic dodecahedron. B-D from Bourne et al.7i...

Figure 42 The structure of apoferritin. N = N-terminus protein helices E form hydrophobic channels (reproduced with permission from Adv. Inorg. Biochem., 1984, 5, 39, Elsevier, Amsterdam)...

Ferritin has also been compared with iron-dextran by the EXAFS technique.1108 The apoferritin controls the deposition of the core. Reconstitution of ferritin under a range of conditions always gives the same structure, which is not the case in the absence.of apoferritin. There are metal-binding sites on the protein shell. There is evidence for the binding of iron to apoferritin, probably by carboxyl groups, but there is little detailed information on these sites.1098 On the other hand, other metal ions inhibit the formation of ferritin and may do this by binding at or close to the iron sites. Of most significance appear to be results on Tb3+, Zn2+ and V02+,... 

X-ray diffraction studies at 3.0 A resolution have indicated the presence of two neighbouring manganese atoms (3.6-0.3 A) in each subunit (Barynin et al., 1986). Unlike the iron catalases, the Mn-catalases contain no heme and the active centres have an unusual structure. The subunit skeleton is a bundle of four nearly parallel helices, two of which are ca. 40 A long. There are similarities to the structure of apoferritin, however, the polypeptide chain in Mn-catalase is twice that of apoferritin. 

The most commonly biopolymers separated by Fl-FFF are proteins [49]. Fl-FFF is capable of separating proteins differing by just 15% in size within 3 to 10 min. S-Fl-FFF has been applied to a variety of proteins, including albumin, ovalbumin, y-globulin, hemoglobin, ferritin, lysozyme, [1-casein, apoferritin, human and rat blood plasmas and elastin [41,240,247]. Fl-FFF was also used to investigate the structural transformations of proteins [240]. 

Very low-angle X-ray data (26 A resolution) of horse spleen apoferritin fit approximately the Fourier transform of a uniform spherical shell with inner and outer diameters of 76 and 122 A (92, 95). Low-angle difference X-ray data for ferritin and apoferritin indicate iron cores of high scattering power that are approximately spherical (d = 78 A) (92). Cubic crystal point symmetry shows that ferritin molecules are composed of 24 structurally equivalent subunits related by 432 symmetry, there being one polypeptide chain per asymmetric unit. In mixed H and L chain copolymers, the apparent structural equivalence must be statistical, although very similar chain conformations are expected. 

The three-dimensional structures of horse spleen apoferritin (85% L, 15% H subunit) (11), rat liver ferritin (66% L, 34% H subunit) (94),... 

Fig. 19.28 Structural features of apoferritin. The gross quaternary structure of the assembled molecule is shown in the center and more details on the fourfold channels (left), the threefold channels (upper right) and the subunits (lower right) are also illustrated. [From Harrison,...

FIGURE 22.13 (a) Structure of Gd-HPD03A. (b) Schematic representation of the dissociation of apoferritin into subunits at pH 2, followed... 

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