title: The thermodynamic and binding properties of the transferrins as studied by isothermal titration calorimetry.
abstract: BACKGROUND
  In mammals, serum-transferrins transport iron from the neutral environment of the blood to the cytoplasm by receptor-mediated endocytosis. Extensive in-vitro studies have focused on the thermodynamics and kinetics of Fe(3+) binding to a number of transferrins. However, little attention has been given to the thermodynamic characterization of the interaction of transferrin with its receptor.
  
  
  METHODS
  Iron-loaded transferrin (Tf) binds with high affinity to the specific transferrin receptor (TfR) on the cell surface. The Tf-TfR complex is then internalized via receptor mediated endocytosis into an endosome where iron is released. Here, we provide an overview of recent studies that have used ITC to quantify the interaction of various metal ions with transferrin and highlight our current understanding of the thermodynamics of the transferrin-transferrin receptor system at physiological pH.
  
  
  CONCLUSIONS
  The interaction of the iron-loaded transferrin with the transferrin receptor is a key cellular process that occurs during the normal course of iron metabolism. Understanding the thermodynamics of this interaction is important for iron homeostasis since the physiological requirement of iron must be appropriately maintained to avoid iron-related diseases.
  
  
  CONCLUSIONS
  The thermodynamic data revealed stoichiometric binding of all tested metal ions to transferrin with very high affinities ranging between 10(17) and 10(22)M(-1). Iron-loaded transferrin (monoferric or diferric) is shown to bind avidly (K~10(7)-10(8)M(-1)) to the receptor at neutral pH with a stoichiometry of one Tf molecule per TfR monomer. Significantly, both the N- and the C-lobe contribute to the binding interaction which is shown to be both enthalpically and entropically driven. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.
authors.affiliation: Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA. bouabdf@potsdam.edu
authors.forename: Fadi
authors.initials: F
authors.lastname: Bou-Abdallah
authors.forename: Tyson R
authors.initials: TR
authors.lastname: Terpstra
mesh_terms: D000818:Animals; D002151:Calorimetry / Q000379:methods*; D004705:Endocytosis; D006801:Humans; D007501:Iron / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011990:Receptors, Transferrin / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics; D061250:Transferrins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011990:Receptors, Transferrin; D061250:Transferrins; D007501:Iron