Kinetics of iron release from transferrin bound to the transferrin receptor at endosomal pH

• Published in: Biochimica et biophysica acta Vol. 1820; no. 3; pp. 326 - 333
• Main Authors: Steere, Ashley N., Byrne, Shaina L., Chasteen, N. Dennis, Mason, Anne B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2012
• Subjects: Biological Transport; blood serum; Endocytosis; Endosomes - metabolism; Fluorescence; glycoproteins; Humans; Hydrogen-Ion Concentration; iron; Iron - metabolism; Kinetics; Protein Conformation; Receptors, Transferrin - chemistry; Receptors, Transferrin - metabolism; Transferrin; Transferrin - metabolism; Transferrin receptor; transferrins; TFR; LockChTF; Transferrin; Fluorescence; FeNhTF; Transferrin receptor; LMCT; LockNhTF; FeChTF; KISAB; sTFR; hTF; Kinetics; Fe2hTF
• ISSN: 0304-4165; 0006-3002; 1872-8006; 0006-3002
• DOI: 10.1016/j.bbagen.2011.06.003

Human serum transferrin (hTF) is a bilobal glycoprotein that reversibly binds Fe3+ and delivers it to cells by the process of receptor-mediated endocytosis. Despite decades of research, the precise events resulting in iron release from each lobe of hTF within the endosome have not been fully delineated. We provide an overview of the kinetics of iron release from hTF±the transferrin receptor (TFR) at endosomal pH (5.6). A critical evaluation of the array of biophysical techniques used to determine accurate rate constants is provided. Delivery of Fe3+to actively dividing cells by hTF is essential; too much or too little Fe3+ directly impacts the well-being of an individual. Because the interaction of hTF with the TFR controls iron distribution in the body, an understanding of this process at the molecular level is essential. Not only does TFR direct the delivery of iron to the cell through the binding of hTF, kinetic data demonstrate that it also modulates iron release from the N- and C-lobes of hTF. Specifically, the TFR balances the rate of iron release from each lobe, resulting in efficient Fe3+ release within a physiologically relevant time frame. This article is part of a Special Issue entitled Molecular Mechanisms of Iron Transport and Disorders. ► Because the interaction of transferrin with the receptor controls iron distribution, an understanding of this process essential. ► The transferrin receptor modulates iron release from the N- and C-lobes of human serum transferrin. ► The transferrin receptor balances the rate of iron release from each lobe, resulting in efficient Fe3+ release from transferrin.