FERRITIN STRUCTURE AND ITS BIOMEDICAL IMPLICATIONS.
What is ferritin?
Iron is an essential element for living organisms but
is highly toxic in excess. Living organisms store iron to provide an
appropriate concentration and at the same time to protect themselves against
the toxic effects of iron excess. The major intracellular storage form of iron
is ferritin. Ferritin is the
The structure of ferritin consists of a spherical protein shell (apoferritin) composed of 24 polypeptide subunits (L light or H heavy) chains, surrounding an aqueous cavity with internal and external diameters of about 8 and 12 nm. The multisubunit construction of the apoferritin shell allows the generation of channels. Eight hydrophilic channels of about 4-5 Å would lead to the protein cavity. Water, metallic cations and hydrophilic molecules of appropriate size would diffuse through these channels from the external solution to the cavity or from the cavity to the external solution.
How does ferritin store iron?
Fe2+is oxidized and transported into the ferritin interior and deposited as an iron mineral core, traditionally described as ferrihydrite 5Fe2O3·9H2O), which is attached to the inner wall of the sphere. Up to 4500 Fe can be stored although the normal value is about 2000
How does ferritin release iron?
Two models, not mutually exclusive, have been proposed for recovering ferritin iron in vivo: reduction followed by iron(II) mobilization or direct iron(III) chelation. The first one has been more extensively studied because it has been traditionally considered as the true mechanism.
Still to be solved is the problem of knowing the real structure of the ferritin core. Is it really ferrihydrite or is it a mixture of different iron oxide phases (ferrhydrite one of them)? How really proceeds the in vivo iron removing process?
Anomalous high concentration of iron has been observed in brain in several neurodegenerative diseases. Differences in the ferritin core composition of physiological and pathological human brain of patients with Alzheimer’s disease have been observed. Does ferritin play any role in the development of neurodegenerative disease?
Further studies on ferritin (iron biomineralization, iron core structure, iron removing…) will provide not only greater insight into the knowledge of this “magic” molecule but also will assist in providing answers to the iron metabolism in humans, which is of capital significance for chemistry, biology, medicine, and nutrition.
Such studies are underway in our and other laboratories.
Papers of our group in this field:
A Preliminary-Study on the Interaction of Ferritin Single-Crystals with Chelating-Agents.
JOURNAL OF CRYSTAL GROWTH 1996, 168, 138-141.
Iron(III) complexation of desferrioxamine B encapsulated in apoferritin.
Journal of Inorganic Biochemistry 2004, 98, 469-472.
Catechol releases iron(III) from ferritin by direct chelation without iron(II) production
DALTON TRANSACTIONS 2005, 811-815.
Release of Iron from Ferritin by Aceto- and Benzohydroxamic Acids
INORGANIC CHEMISTRY 2005, 44, 2706-2709.
Rate of Fe2+ Transfer through the Horse Spleen Ferritin Shell Determined by the rate of Formation of Prussian Blue and Fe-desferrioxamine within the Ferritin Cavity. BIOPHYSICAL CHEMISTRY 2006, 120, 96-105.
Why ferritin is interesting in nanoscience and nanotechnology?
The size of ferritin is measured in nanometers (inside diameter: 8 nm; outside diameter: 12 nm). The use of ferritin, as well as other nano- biomacromolecules, is a powerful route for the preparation of metallic nanoparticles because their use allows:
- the control of the particle size: the particle can not be larger than the cavity. The control of size is very important because the properties of particles strongly depend on their size. Classic methods to produce metallic particles often allow the control of the size if this is over 15-20 nm, but this is more complicated below 10nm.
- avoid the agglomerationof particles, because the organic shell (apoferritin) avoid the contact between metal core. This point is obviously crucial because if the particles agglomerate they loose the properties inherent to the size.
- rend the particles water soluble. That is very important to the implementation of the particles for technological applications, either directly, as a solution or as precursors of nanostructured materials by ordered deposition of the particles on a substrate, for example by nanolitography and so on.
- the entire structure of ferritin can be transported into cells by endocytosis.
- Nanoparticles of Prussian-blue Ferritin: A New Route for Obtaining Nanomaterials
Inorganic Chemistry 2003, 42, 6983-6984. - Magnetic Langmuir-Blodgett films of ferritin with different iron loadings.
SYNTHETIC METALS 2005, 148, 7-10. - Langmuir-Blodgett Films Based on Inorganic Molecular Complexes with Magnetic or Optical Properties. Advances in Colloid and Interface Science 2005, 116(1-3), 193-203.
- Preparation of Cu and CuFe Prussian Blue derivative nanoparticles using the apoferritin cavity as nanoreactor.
Dalton Transactions 2005, 2492-2494. - Apoferritin-encapsulated Ni and Co Superparamagnetic Nanoparticles
jOURNAL OF THE MATERIAL CHEMISTRY 2006, 16, 2757-2761. - Magnetic Langmuir-Blodgett Films of ferritin with different iron contents
LANGMUIR 2006, 22, 6993-7000. - Permanent magnetism in apoferritin-encapsulated Pd nanoparticles
jOURNAL OF THE MATERIAL CHEMISTRY 2007, in press.
We are developping new methods to produce metallic nanoparticles by using the apo- and ferritin: zero-valent metal, core-shell bimetallic and bifunctional magnetic-optical nanoparticles.
Papers of our group in this field:
