Please be patient while the structures in the left frame load. In order to display all of the structures in the tour properly, press 'View' buttons below in order (from 1 to the end).
A photograph of microscopic apoferritin crystals obtained by the addition of polyethylene glycol. [1]
This is the wireframe display of ferritin, extracted from the bacteria Escherichia Coli . Ferritins are a family of proteins found in animals, plants and bacteria and have the function of storing iron. They are found in the liver, spleen and bone marrow of animals. When iron is set free from its transporting system (see the tour of Transferrin) and released within a cell, it has to be either directly used or stored because free iron can react with dioxygen to produce hazardous radicals:
Fe(II) + O2 Fe(III) + O2-. (1)
Fe(II) + H2O2 Fe(III) + OH- + OH. (2)
The O2-. and OH. radicals are highly reactive and can damage the genetic material in the cell nucleus. The transport and the storage of iron must be rapid and reversible under physiological conditions.
One part of the ferritin molecule is highlighted. The hollow sphere, with a rhombic dodecahedral symmetry, is very apparent in this display. It has an outer diameter of 13 nm and an inner diameter of approximately 7.5 nm. This very large protein assembly has a molecular weight of 440 kDaltons in its apo form and holds up to 4500 Fe atoms.
This display of ferritin highlights only two of the twenty-four equivalent subunits which arrange to form a hollow sphere. The spatial arrangement of all the subunits is important in that it allows channels to form along the threefold and fourfold axes (see below).
This display shows two subunits. Each subunit consists of four long, parallel alpha helices, forming a bundle, and a fifth short alpha helix arranged perpendicularly (yellow). There are four iron ions that are coloured orange (see the next stop for a detailed view). There is a heme group in bacterial ferritin that connects the two subunits through sulphurs from Met 52 (coloured green) from both chain A and B. Like myoglobin, it contains porphyrin b and the subunits are sometimes referred to as a cytochrome b1. The ferritin molecules from other organisms, like humans, lack this heme group (but they do contain the diiron nucleation centre). The heme might serve to assist the self-assembly of the protein sphere by acting as a connector between the two subunits. It could also function as an electron carrier, shuttling electrons from reducing agents outside the sphere to the diiron-dioxygen reduction centre.
This display shows the metal centres. The ribbon has been omitted in order for the metal centres to be more clearly displayed. These centres are not described in depth in the literature. The bridging carboxylate ligands are similar to those found in hemerythrin and methane monooxygenase (both can be found in the Guided Tours of Metalloproteins). It is assumed that this 2-Fe2+ site binds O2 to produce the unstable complex
(his)(glu)FeIII( µ-OO2-)( µ-glu)2FeIII(his)(glu)
Hydrolysis of this complex gives (H2O)xFeIIIOFeIII(OH2)x which is released into the cavity where Fe(III) further hydrolyses to start the nucleation of the ferrihydrite mineral.
4Fe3+ + 8H2O 4Fe(O)OH + 12H+
This reaction shows that ferritin is a pH buffer as well as an Fe buffer.
This display shows the three-fold channels. Once the nucleation starts, more material is required. The iron, as Fe2+, enters the protein through three-fold channels.
These channels are coated with aspartate and glutamate carboxylates. The small red spheres lining the wall of the channel are the oxygen atoms from aspartate and glutamate. They make the channels hydrophilic. The glutamate residues help to catalytically oxidize Fe(II) on the surface of the mineral:
4Fe2+ + O2 + 6H2O 4Fe(O)OH + 8H+.
This process results in the formation of well-defined crystals of up to 75 Å in diameter.
This display shows the four-fold channels. When the iron has to be released from ferritin, reduced flavins enter the hydrophobic four-fold channels. Reduced iron exits the protein core through the three-fold channels.
The ferritin model complexes are synthesized and studied in order to elucidate the formation, structure and properties of the iron oxyhydroxide mineral that is formed inside the protein. In addition they are interesting nano-scale objects and they provide information on the formation of rust.
The structure in the left frame is such a model compound. It is a hexanuclear aggregate [Fe6( µ4-O)2( µ2-OMe)8(OMe)4(tren)2]2+ (tren = 2,2',2''-triaminotriethylamine, N(CH2CH2NH2)3) [2]. It is formed as an orange crystalline solid by solvolytic aggregation when a solution of Fe(CF3SO3)2 and tren in methanol is exposed to air.
This structure is the first to contain a µ4-O2- ligand.
The iron ions sit in the octahedral holes formed by either oxygen atoms.
or oxygen (red) and nitrogen (blue) atoms. Thus the whole structure resembles a fragment of the layered structure common in iron oxides.
If you would like to see more models for the mineral formed inside the ferritin cavity see:
Understanding the crystallization of minerals inside the ferritin cavity has lead to important advances in the synthesis of nanomaterials. Apoferritin can serve as a perfect "reaction vessel" for the growth of crystalline nanoparticles of CdS or ZnS of well-defined size. For the first steps towards such a synthetic procedure see Science (261), 1286 (Sept. 3, 1993).