Ferritin

1
Ferritin

• Cennyana Boon
• Peter Greene
• Juwina Wijaya

2
Storage Protein

• Stores small molecules and ions.
• Found in ovalbumin in egg whites for development
  of bird embryo, casein in milk.
• Metal-ion storage protein e.g. ferritin,
  metallothionein.
• Store metal ions such as Fe, Zn, Cd and Cu for
  efficiency and prevent toxicity.

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Metal Ion Storage Proteins

• 2 main strategies
• Metal ion bound by cytoplasmic proteins or
  macromolecules
• Metal ion transported into membrane-bound
  compartments within the cell

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Importance of Iron

• O2 transport e.g. hemoglobin, myoglobin
• Electron transport e.g. cytochrome c
• Cellular Growth e.g embryonic development,
  chloroplast maturation, seed germination.

5
Ferritin

• Iron-storage protein.
• - Store as much as 4500 Fe atoms in a single
  molecule.
• Found in higher plants and animals.
• Consists of 24 polypeptide subunits with a-helix
  motifs.
• - Size of one subunit about 20 kDa
• Spherical molecule that contains Fe2O3 in the
  inner core.
• - Apoferritin

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Ferritin (contd)

• Symmetrical 2-, 3-, 4- fold axes.
• 8 pores acting as ion channels for Fe2 into the
  cavity.
• Each pore is found in the junction of 3 subunits.

Fig. VIII.2.1a
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Ferritin subunits

• 2 types of subunits
• H- subunit
• L- subunit ( noncatalytic and found only in
  animals)
• Ratio of HL reflects the activity of iron
  oxidation.

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Other Ferritin Structures

• Bacterioferritin
• - Have 24 subunits up to 12 heme groups
• Miniferritin (dps proteins)
• - Only 12 subunits.

Code 1JGC
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What does ferritin do?

• Store Fe2 ions in both prokaryotes and
  eukaryotes as an Fe3 mineral.
• Provides Fe for biological functions

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Biological Inorganic Chemistry pp.1
How Does Ferritin Work?

• Ferroxidase is the enzyme that catalyzes the
  mineralization reaction
• Note Translocation of hydrated Fe3 mineral
  precursor to protein shell to the cavity and into
  mineral requires minutes to hours. Meanwhile,
  oxidation and decay of the mineral precursor
  occurs in milliseconds

11
How Does Ferritin Work?

• Iron can be released from Ferritin when needed
• Not a simple ferric oxide hydration and reduction
  of Fe3 ? Fe2
• Two current hypotheses
• Destroy and Dissolve
• Unfolding/opening the ferritin pores

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Ferritin Demineralization Destroy and Dissolve

• Compartmentalization of Ferritin inside the
  lysosome
• Digestion of the ferritin protein
• Dissolution of the mineral
• Export of the iron ions

13
Ferritin DemineralizationUnfolding/Opening of
the ferritin pores

• Gates of ferritin pores can open or unfold
• Reductants and chelators now have increased
  access to ferritin iron mineral
• Iron mineral removal increase by 30fold
• Rate of mineral reduction and chelation increase
  without changes in global structure of function

Biological Inorganic Chemistry pp.1
14
Selective Advantage of Ferritin Pores

• Pores protect ferritin minerals from excess
  reductants in the cell
• Pores are embedded in two layers of polypeptide
  helices stabilized by hydrophobic interactions,
  analogous to a lipid bilayer, to form a protein
  sphere