Biomineralisation - Biological Inorganic Chemistry - page 364

The substrates involved in ferritin iron deposition (Fe 2 þ ,Fe 3 þ ,O 2 ,) gain access to the interior of the apoferritin
protein shell through the threefold channels. Calculations of electrostatic potential in HuHF show that the negative
outer entrance is surrounded by patches of positive potential and that this attracts cations towards the channel
entrance. The role of the threefold channel in the entry of divalent cations into the interior of the protein is
underlined by our studies on recombinant human H-chain ferritin (rHuH); which show the way Zn 2 þ ions can
transit through this channel, using the configurational flexibility of a key cysteine residue to move the ion through
the channel ( Figure 19.5 ), in a manner reminiscent of transit through the potassium channel described in
Chapter 9. Zn(II) was used as a redox-stable alternative for Fe(II).
FIGURE 19.5 In the Zn derivative crystal structures, the channel aligned on the 3-fold symmetry axis shows binding to three zinc atoms and
their symmetrically related subunits; the first is in the entrance of the funnel-shaped channel (in cyan), the second is in an alternative position (in
blue), and the third is aligned on the 3-fold axis (in gray). The two representations are in two different orientations; (a) is aligned on the 3-fold
axis and (b) is perpendicular to the axis. (From Toussaint, Bertrand, Hue, Crichton, & Declercq, 2007 . Copyright 2007 with permission from
Elsevier.)
Fe(II) must then move from the 12 ˚ long channel, and traverse a further distance of about 8 ˚ along
a hydrophilic pathway from the inner side of the three-fold channel to the ferroxidase site, and a putative pathway
for Fe(II) is shown in Figure 19.6 . The diiron ferroxidase centre is located in the central region of the four-helix
subunit bundle and the coordination geometry of the ferroxidase centre of human H-chain ferritin is shown in
Figure 19.7 . Detailed analysis of the ferroxidase reaction in H-chain ferritin has allowed the identification of
a number of intermediates, which are illustrated in Figure 19.8 .
While the initial stage of iron incorporation in mammalian ferritins requires the ferroxidase sites of the
H-chains, thereafter the inner surface of the protein shell of the L chains provides nucleation sites which supply
ligands that can partially coordinate iron but which leave some coordination spheres available for mineral phase
anions. This enables the biomineralisation process to proceed, with formation of one or more small polynuclear
ferrihydrite crystallites, which can then act as nucleation centres for mineral growth. Most probably, one of these
clusters will become the dominant nucleation centre and growth of the mineral would then occur from this centre.