Ferritin bacterioferritin

Ferritin, bacterioferritin Vertebrates, bacteria Ferroxidase ( ) EX34EX2HX4lEX36E ... 

Figure 6.2 Phylogenetic tree showing the evolutionary relationship between members of the ferritin-bacterioferritin-rubreyrthrin superfamily. Reprinted from Harrison et ah, 1998, by courtesy of Marcel Dekker, Inc.

Table 6.1 Amino-acid sequence alignment of four mammalian ferritins (Horse L chain, HoL Human L chain, HuL Human H chain, HuH Rat H, RaH) and of one of the ferritins, FTN, and the bacterioferritin, BFR of...

Their subunits are folded in a central bundle of four a-helices, which assemble to form a roughly spherical protein shell surrounding a central cavity within which iron is stored (up to 4500 iron atoms per 24mer in ferritins and bacterioferritins, and around 500 in the smaller Dps protein 12mer). 

Iron is stored in these proteins in the ferric form, but is taken up as Fe2+, which is oxidized by ferroxidase sites (a more detailed account of iron incorporation into ferritins is given later in this chapter). As we point out in Chapter 13, ferritins are members of the much larger diiron protein family. After oxidation, the Fe3+ migrates to the interior cavity of the protein to form an amorphous ferric phosphate core. Whereas the ferritins in bacteria appear to fulfil the classical role of iron-storage proteins, the physiological role of bacterioferritins is less clear. In E. coli it seems unlikely that bacterioferritin plays a major role in iron storage. 

About a quarter of the total body iron is stored in macrophages and hepatocytes as a reserve, which can be readily mobilized for red blood cell formation (erythropoiesis). This storage iron is mostly in the form of ferritin, like bacterioferritin a 24-subunit protein in the form of a spherical protein shell enclosing a cavity within which up to 4500 atoms of iron can be stored, essentially as the mineral ferrihydrite. Despite the water insolubility of ferrihydrite, it is kept in a solution within the protein shell, such that one can easily prepare mammalian ferritin solutions that contain 1 M ferric iron (i.e. 56 mg/ml). Mammalian ferritins, unlike most bacterial and plant ferritins, have the particularity that they are heteropolymers, made up of two subunit types, H and L. Whereas H-subunits have a ferroxidase activity, catalysing the oxidation of two Fe2+ atoms to Fe3+, L-subunits appear to be involved in the nucleation of the mineral iron core once this has formed an initial critical mass, further iron oxidation and deposition in the biomineral takes place on the surface of the ferrihydrite crystallite itself (see a further discussion in Chapter 19). 

Typically, mammalian ferritins can store up to 4500 atoms of iron in a water-soluble, nontoxic, bioavailable form as a hydrated ferric oxide mineral core with variable amounts of phosphate. The iron cores of mammalian ferritins are ferrihydrite-like (5Fe203 -9H20) with varying degrees of crystallinity, whereas those from bacterioferritins are amorphous due to their high phosphate content. The Fe/phosphate ratio in bacterioferritins can range from 1 1 to 1 2, while the corresponding ratio in mammalian ferritins is approximately 1 0.1. 

Why mammalian ferritin cores contain ferrihydrite-like structures rather than some other mineral phase is less easy to understand, and presumably reflects the way in which the biomineral is built up within the interior of the protein shell together with the geometry of the presumed nucleation sites. The phosphate content in the intracellular milieu can readily be invoked to explain the amorphous nature of the iron core of bacterioferritins and plants. Indeed, when the iron cores of bacterioferritins are reconstituted in the absence of phosphate, they are found to be more highly ordered than their native counterparts, and give electron diffraction lines typical of the ferrihydrite structure. Recently it has been reported that the 12 subunit ferritin-like Dps protein (Figure 19.6), discussed in Chapter 8, forms a ferrihydrite-like mineral core, which would seem to imply that deposition of ferric oxyhydroxides within a hollow protein cavity (albeit smaller) leads to the production of this particular mineral form (Su et al., 2005 Kauko et al., 2006). 

Probing Structure-Function Relations in Ferritin and Bacterioferritin... 

Probing Structure-Function Relations in Ferritin and Bacterioferritin P. M. Harrison, S. C. Andres. P. J. Artymiuk, G. C. Ford, J. R. Guest,... 

Some respiratory nitric oxide (NO) reductases, which contain a mixed dinuclear heme, nonheme iron site see Cytochrome Oxidase), and [2Fe-2S] ferredoxins see Iron-Sulfur Proteins), are covered in separate chapters of this encyclopedia. Ferritins and bacterioferritins, which contain a metastable nonheme diiron site are also covered elsewhere in this Encyclopedia see Iron Proteins for Storage Transport their Synthetic Analogs). Another chapter in this encyclopedia, Iron Models of Proteins with Dinuclear Active Sites, provides a synthetic perspective on the properties of nonheme, non-sulfur diiron sites in proteins. Recent reports of synthetic polypeptides that contain nonheme, non-sulfur diiron sites should also be noted. 

Another member of the ferritin family found in bacteria is bacterioferritin (BFR). BFR has the same 24-meric... 

There are a variety of types of ferritin nonheme iron core, ranging from the highly ordered cores of horse spleen ferritin to the amorphous cores of bacterioferritins. As noted... 

EXAFS studies of A. vinelandii bacterioferritin have shown that there are fewer Fe-Fe contacts in the mineral core than occur with native horse ferritin, and those that do occur are at a greater interatomic distance. Moreover, the EXAFS data showed that the core iron of bacterioferritin had 5 to 6 phosphorus atoms no more than 3.17 A distant, thus supporting a model for the core of an amorphous Fe(III)-phosphate complex in which some of the phosphate bridges Fe(III) ions and some of it is nonbridging. 

Reconstitution experiments with apoferritins from animal and bacterial sources, whose native iron-loaded ferritins had crystalline and amorphous cores respectively, have been informative in showing that the core morphology is not determined by the protein shell. For example, Baaghil et al and Mann etalP were able to form crystalline cores in bacterioferritins, and Rohrer formed cores of iron-... 

The mechanism of iron oxidation and core formation in Dps differs from that of ferritin and bacterioferritin in that the rate of minerahzation is faster than oxidation at the ferroxidase center in L. innocua ferritin and E. coli Dps core formation is 60% faster than the ferroxidation reaction. ... 

The predominant class of intracellular iron-storage compounds is represented by ferritin in eukaryotes and bacterioferritin in prokaryotes (see Iron Proteins for Storage Transport their Synthetic Analogs). In various in vivo Mdssbauer spectroscopic studies on siderophore uptake in fungi, it was realized that siderophores can also function as intracellular iron-storage compounds. In the ascomycete Neurospora crassa, the transport siderophore coprogen represents an intracellular transient iron pool. A major part of coprogen-bound iron is transferred to a... 

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