title: Primary receptor-recognition site of human transferrin is in the C-terminal lobe.
abstract: The role of the transferrin receptor in capturing and conveying transferrin through the cell during the iron-donating cycle of receptor-mediated endocytosis has been studied extensively. Nevertheless, almost nothing is known of how human transferrin binds to its receptor. In an initial approach toward delineating the receptor-recognition site(s) of human transferrin, we have studied the interactions of proteolytically-cleaved, single-sited fragments of transferrin, representing the N- and C-lobes of the molecule respectively, with cells expressing the transferrin receptor on their plasma membranes. Only the C-fragment was found capable of donating iron to hepatoma-derived HuH-7 cells or of binding to surface receptors of HuH-7 and leukemic K562 cells. Although no association of N- and C-fragments could be demonstrated by gel chromatography, the presence of excess N-fragment strengthened the binding of C-fragment by an order of magnitude. An explanation of these observations is that the primary receptor recognition site of human transferrin is on the C-lobe of the protein, but that prior binding of this lobe to receptor enables the N-lobe to respond to receptor as well, either directly or by interaction with the bound C-lobe.
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: O
authors.initials: O
authors.lastname: Zak
authors.forename: D
authors.initials: D
authors.lastname: Trinder
authors.forename: P
authors.initials: P
authors.lastname: Aisen
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D006868:Hydrolysis; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism*; D013820:Thermolysin; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D010446:Peptide Fragments; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron; D013820:Thermolysin