C4
3 x C4 axes
4 x C3 axes
O symmetry
(no mirror planes)
C3
C4
C4
C3
Fe3+Ox(OH)y core
C4
One bundle
C3
C4
Fe3+O(OH)
Fe2+ oxid
Fe2+ exit
C3
24 subunuits of
4 a-helix bundles
Like an iron malted milk ball!
Fact: At pH 7, [Fe3+] = 10-18 M why?
• Ferritin manages to concentrate ferric ion to mM concentrations (10-3 M).
• Lack of gene for ferritin lethal.
The reaction
2000 Fe2+(H2O)6 + O2  1000 Fe3+—O-O—Fe3+ 2000 Fe3+(H2O)6 + H2O2
fast, msec
slow, minutes or hours
Enters at C3 pores;
‘translocating mineral precursor’
rxn occurs in subunits
Fe3+2O3(H2O)1000 + 5000 H+
Exits from C3 pores
How and where iron exits from ferritin for
cellular use is uncertain.
Proline substitution for conserved leucine
134 (L134P) allowed normal assembly but
increased iron exit rates. X-ray
crystallography of H-L134P ferritin
revealed localized unfolding at the 3-fold
axis, also iron entry sites, consistent with
shared use sites for iron exit and entry. The
junction of three ferritin subunits appears
to be a dynamic aperture with a "shutter"
that cytoplasmic factors might open or
close to regulate iron release in vivo.
Localized unfolding at the junction of three ferritin
subunits. A mechanism for iron release?
Takagi, H., Shi, D., Ha, Y., Allewell, N.M., Theil, E.C.
(1998) J.Biol.Chem. 273: 18685-18688