title: Transferrin-mediated cellular iron delivery.
abstract: Essential to iron homeostasis is the transport of iron by the bilobal protein human serum transferrin (hTF). Each lobe (N- and C-lobe) of hTF forms a deep cleft which binds a single Fe(3+). Iron-bearing hTF in the blood binds tightly to the specific transferrin receptor (TFR), a homodimeric transmembrane protein. After undergoing endocytosis, acidification of the endosome initiates the release of Fe(3+) from hTF in a TFR-mediated process. Iron-free hTF remains tightly bound to the TFR at acidic pH; following recycling back to the cell surface, it is released to sequester more iron. Efficient delivery of iron is critically dependent on hTF/TFR interactions. Therefore, identification of the pH-specific contacts between hTF and the TFR is crucial. Recombinant protein production has enabled deconvolution of this complex system. The studies reviewed herein support a model in which pH-induced interrelated events control receptor-stimulated iron release from each lobe of hTF.
authors.affiliation: Department of Biochemistry, University of Vermont, College of Medicine, Burlington, VT, USA.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Luck
authors.forename: Anne B
authors.initials: AB
authors.lastname: Mason
mesh_terms: D000838:Anions / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011990:Receptors, Transferrin / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000838:Anions; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D014168:Transferrin; D007501:Iron