Structure/Function Overview of Proteins Involved in Iron Storage and Transport

Abstract

Iron, the major trace element in the body, is an essential component of many proteins and enzymes. As low-molecular-weight iron is potentially toxic to cells, higher organisms express a number of proteins for the transport and storage of iron. We review our current understanding of the intestinal absorption of iron in the light of recently identified membrane proteins, namely the ferrric reductase, Dcytb, the two iron(II) transport proteins, DMT1 and ferroportin/Ireg1, and hephaestin, the membrane-bound homologue of the ferroxidase ceruloplasmin. Two types of mammalian transferrin receptor, TfR1 and TfR2, are now known to exist. The structure of TfR1 and its role in the process of receptor-mediated cellular uptake of iron are presented together with structural information on the iron storage protein ferritin. Mechanisms for the regulation of levels of TfR1 and ferritin, as well as other proteins involved in iron homeostasis, are discussed. Our current knowledge and understanding of the structure of members of the transferrin family of iron-binding proteins and the nature of the iron-binding centres in transferrins is presented, together with information on the processes of iron-uptake and iron-release by transferrin and a summary of the elements that have been found to bind to transferrins.

Functional Anthology of Intrinsic Disorder. 3. Ligands, Post-Translational Modifications, and Diseases Associated with Intrinsically Disordered Proteins

“…For example, besides the well-known heme-containing proteins (cytochromes, myoglobin and hemoglobin), transferrins, lactoferrin, ceruloplasmin and ferritins, numerous other proteins are involved in iron homeostasis. 65 The vast majority of these iron-binding proteins are known to possess well-organized rigid structure. Similarly, iron-sulfur or 4Fe-4S cluster containing proteins are almost always highly organized, as these clusters are perhaps the most abundant and the most diversely employed cofactor.…”

Altered expression of the iron transporter Nramp1 (Slc11a1) during fetal development of the retinal pigment epithelium in microphthalmia-associated transcription factor Mitfmi and Mitfvitiligo mouse mutants

“…However, tight control of cellular iron homeostasis is necessary to avoid an excess of "free" iron, because trace amounts of iron can catalyze the production of highly toxic free radicals via the Fenton reaction, leading to oxidative damage. Several proteins are involved in the regulation of cellular uptake, transport, storage and export of iron (Sargent et al, 2005) (see FIGURE 8). Iron circulates in the blood bound to transferrin.…”

“…As the internalized endosome undergoes acidification, Fe +3 is released from transferrin, and reduced to Fe +2 by endosomal ferric reductase. Although Nramp2 expression/function has not yet been characterized in the eye, ferrous ion (Fe +2 ) is very likely transported out of the endosome and into the cytosol in RPE cells by Nramp2, and the transferrin receptor complex recycled back to the basolateral cell surface (Sargent et al, 2005). Cytosolic ferrous ion entering the labile iron pool can be utilized for several critical cellular functions.…”

Iron-related transcriptomic variations in Caco-2 cells: In silico perspectives

“…In mammals, there is no active excretion mechanism for iron. Indeed, absorption is the most important regulation process of iron homeostasis [2]. It takes place in the small intestine (duodenum, upper jejunum) in enterocytes and its control is a complex process that cannot be fully explained with present knowledge [3].…”