458 IRON-CONTAINING PROTEINS AND ENZYMES
as iron - responsive elements (IREs). Strong interaction between IRPs and
IREs assures proper iron homeostasis in animal cells under iron shortage.
Conversely, under iron - replete conditions, IRP1 binds a [4Fe – 4S] cluster and
functions as cytosolic aconitase. Comparison with known structures of other
aconitase enzymes reveals conserved folds and active site environments
throughout the aconitase superfamily.
7.9.3 Iron – Oxo Proteins
A second large class of non - heme iron proteins contains iron - oxo clusters. Two
of these are (1) transferrins for metal transport and (2) ferritins for metal
storage. Transferrins are eukaryotic iron - binding glycoproteins that control the
level of free iron in biological fl uids. Transferrin proteins, loaded with Fe(III)
ions, encounter transferrin receptors on cell surfaces, bind to the receptor, and
are transported into cells via a vesicle. Inside the cell, the vesicle is acidifi ed,
causing transferrin to release its iron ions. The receptor is then transported
through the endocytic cycle back to the cell surface, ready for another round
of iron uptake. Each transferrin molecule has the ability to carry two Fe(III)
ions. The Wellcome Trust Sanger Institute website for transferrin is found at
http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF00405.
Ferritins are globular protein complexes, usually consisting of 24 protein
subunits, forming a hollow, roughly spherical three - dimensional shape. They
are the main intracellular iron storage proteins in both prokaryotes and
eukaryotes, keeping iron ions in a soluble and nontoxic form. Each ferritin
24 - mer can hold up to 4500 iron atoms or ions. Some ferritins are heavy (H) -
chain rich; the H - chains catalyze oxidation of Fe(II). Some ferritins are light
(L) - chain rich; the L - chains promote nucleation and storage of Fe(III) ions.
Recent X - ray crystallographic studies of L - chain human ferritin have been
carried out^174 (PDB: 2FFX, 2FG4, 2FG8). Human H - chain ferritins have been
studied as well and compared to horse H - chain ferritins^175 (PDB: 1AEW
(horse), 2FHA (human)).
A website - based ferritin tutorial, last updated in 1998, can be
found at http://www.chemistry.wustl.edu/ ∼ edudev/LabTutorials/Ferritin/
FerritinTutorial.html. The website is accompanied by a Journal of Chemical
Education publication describing ferritin and a general chemistry laboratory
experiment for analysis of the iron content of ferritin.^176 The Wellcome Trust
Sanger Institute ferritin website is at http://www.sanger.ac.uk//cgi-bin/Pfam/
getacc?PF00210. M. A. Carrondo has written a review of bacterioferritins —
ferritins isolated from bacteria, some of which contain heme iron centers.^177
Stephen J. Lippard ’ s group has synthesized and characterized mixed - valent
dodecairon oxo complexes that are models for the biomineralization of ferri-
tin. The iron - oxo clusters exhibited properties of both discrete molecules and
extended solids and were deemed to be representative of a new class of nano-
meter - sized compounds bridging the molecular solid - state boundary.^178 Infor-
mation on the X - ray crystallographic structure and electronic properties of