Anion binding properties of the transferrins. Implications for function

Abstract

BackgroundSince the transferrins have been defined by the highly cooperative binding of Fe3+ and a carbonate anion to form an Fe–CO3–Tf ternary complex, the focus has been on synergistic anion binding. However, there are other types of anion binding with both apotransferrin and diferric transferrin that affect metal binding and release. Scope of reviewThis review covers the binding of anions to the apoprotein, as well as the formation and structure of Fe–anion–transferrin ternary complexes. It also covers interactions between ferric transferrin and non-synergistic anions that appear to be important in vivo. General significanceThe interaction of anions with apotransferrin can alter the effective metal binding constants, which can affect the transport of metal ions in serum. These interactions also play a role in iron release under physiological conditions. Major conclusionsApotransferrin binds a variety of anions with no special selectivity for carbonate. The selectivity for carbonate as a synergistic anion is associated with the iron binding reaction. Conformational changes in the binding of the synergistic carbonate and competition from non-synergistic anions both play a role in intracellular iron release. Anion competition also occurs in serum and reduces the effective metal binding affinity of Tf. Lastly, anions bind to allosteric sites (KISAB sites) on diferric transferrin and alter the rates of iron release. The KISAB sites have not been well-characterized, but kinetic studies on iron release from mutant transferrins indicate that there are likely to be multiple KISAB sites for each lobe of transferrin. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.