Nucleation biomineralization

The initial stages of iron incorporation requires the ferroxidase sites of the protein. Thereafter the inner surface of the protein shell provides a surface which supplies ligands that can partially coordinate iron but which leave some coordination spheres available for mineral phase anions, thereby enabling the biomineralization process to proceed, with formation of one or more polynuclear ferrihydrite crystallites. Iron is transferred from the ferroxidase sites to the core nucleation sites by the net reaction (Yang et ah, 1998) ... 

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). 

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). 

The formation of the solid phase (nucleation, precipitation, crystal growth, biomineralization) ... 

The ratio of the instantaneous solute concentration c to the solute s solubility s, where the latter is the solute concentration in equihbrium with its crystalline or precipitated phase. Hence, RS = c/s, and a supersaturated solution experiences a thermodynamic driving force (AG = RT ln[RS]). A supersaturated solution will remain as a metastable state, because crystallization or precipitation requires a mechanism for relieving the supersaturated condition (eg., nucleation or addition of crystallite/precipitate). See Biomineralization... 

ACTIN ASSEMBLY KINETICS BIOCHEMICAL SELF-ASSEMBLY BIOMINERALIZATION PRION PLAQUE FORMATION Nucleation as a highly cooperative process, MICROTUBULE ASSEMBLY KINETICS... 

Crenshaw, M. A. Ionotropic Nucleation by Molluscan Shell Matrix. In The 3rd Internat. Symp. Mechanisms of Biomineralization in the Invertebrates and Plants, Kashikojima,... 

In almost all instances of biological mineralization fibrous proteins represent the bulk of the organic matrix. In the past, this phenomenon has been interpreted to mean that proteins such as collagen, keratin or elastin are the key elements in mineralization by providing nucleation sites and at the same time offering structure and space for oriented crystal growth. However, with the advance in the field of biomineralization this model came under severe attack. At present, there is no universal concept which could explain all the intriguing facets of phosphate deposition in cellular systems. 

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