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C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes O symmetry (no mirror planes)

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Page 2: C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes  O symmetry (no mirror planes)
Page 3: C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes  O symmetry (no mirror planes)
Page 4: C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes  O symmetry (no mirror planes)
Page 5: C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes  O symmetry (no mirror planes)

C4

C4

C4

C3

C3

3 x C4 axes4 x C3 axes O symmetry(no mirror planes)

Page 6: C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes  O symmetry (no mirror planes)

24 subunuits of4 a-helix bundles

Like an iron malted milk ball!

Fe3+Ox(OH)y core

One bundle

Fe3+O(OH)

Fe2+ oxid

Fe2+ exit

C4

C4

C3

C3

Page 7: C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes  O symmetry (no mirror planes)

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.

Fe3+2O3(H2O)1000 + 5000 H+

Exits from C3 pores

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

Page 8: C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes  O symmetry (no mirror planes)

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

Page 9: C4C4 C4C4 C4C4 C3C3 C3C3 3 x C 4 axes 4 x C 3 axes  O symmetry (no mirror planes)