Bacterioferritins

Labarre JF (1978) Conformational Analysis in Inorganic Chemistry Semi-Empirical Quantum Calculation vs. Experiment. 35 1-35 Lammers M, Follmann H (1983) The Ribonucleotide Reductases A Unique Group of Metalloenzymes Essential for Cell Proliferation. 54 27-91 Le Brun NE, Thomson AJ, Moore GR (1997) Metal Centres of Bacterioferritins of Non-Heam-Iron-Containing Cyrochromes 6557. 88 103-138... 

Figure 6.8 Stereoscopic view of the dimeric building block of bacterioferritin (a) twofold axis horizontal (b) twofold axis approximately normal to the page. The protein is represented by a blue a-carbon trace, the haem by a stick model (pink) and the dinuclear metal site by dotted spheres (orange and yellow). From Frolow et ah, 1994. Reproduced by permission of Nature Publishing Group.

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

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...

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.

Chen, C.-Y. and Morse, S. A. (1999). Neisseria gonorrhoeae bacterioferritin structural heterogeneity, involvement in iron storage and protection against oxidative stress, Microbiology, 145, 2967-2975. 

Figure 8.1 Structures of the 24-meric bacterioferritin and the 12-meric Dps protein from E coli, approxoimately to scale. (From Andrews et al., 2003. Reproduced with permission from Blackwell Publishing Ltd.)...

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). 

Figure 13.25 Three-dimensional structures of diiron proteins. The iron-binding subunits of (a) haemery-thrin, (b) bacterioferritin, (c) rubryerythrin (the FeS centre is on the top), (d) ribonucleotide reductase R2 subunit, (e) stearoyl-acyl carrier protein A9 desaturase, (f) methane monooxygenase hydroxylase a-subunit. (From Nordlund and Eklund, 1995. Copyright 1995, with permission from Elsevier.)...

Figure 13.26 Dioxygen-utilizing carboxylate-bridged diiron centres (a) Oxidized (top) and reduced (bottom) MMOH (b) oxidized (top) and Mnn-reconstituted ToMOH (bottom) (c) oxidized (top) and reduced (bottom) RNR-R2 (d) oxidized (top) and reduced (bottom) rubryerythrin (e) reduced stearoyl-acyl carrier protein A9 desaturase (f) reduced bacterioferritin (g) methaemerythrin. Fel is on the left and Fe2 on the right. (Reprinted with permission from Sazinsky and Lippard, 2006. Copyright (2006) American Chemical Society.)...

In the diiron active sites of RNR-R2, A9 desaturase, bacterioferritin and rubrerythrin the flanking carboxyl ligands on the opposite side of the diiron centre are all quite different,... 

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). 

Garg RP, Vargo CJ, Cui X, Knrtz DM Jr. 1996. A [2Fe-2S] protein encoded by an open reading frame upstream of the E. coli bacterioferritin gene. Biochemistry 35 6297-301. 

Quail MA, Jordan P, Grogan JM, et al. 1996. Spectroscopic and voltammetric characterization of the bacterioferritin-associated ferredoxin from Escherichia coli. Biochem Biophys Res Commun 229 635 2. 

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