Differential dissociation kinetics explain the binding preference of insulin-like growth factor binding protein-6 for insulin-like growth factor-II over insulin-like growth factor-I

Insulin-like growth factor binding protein-6 binds insulin-like growth fact or-II with a marked preferential affinity over insulin-like growth factor-I . The kinetic basis of this binding preference was studied using surface pl asmon resonance. Binding of insulin-like growth factor-I and insulin-like g rowth factor-II to immobilized insulin-like growth factor binding protein-6 fitted a two-site binding kinetic model. Insulin-like growth factor-I and insulin-like growth factor-II association rates were similar whereas the di ssociation rate was similar to 60-fold lower for insulin-like growth factor -II, resulting in a higher equilibrium binding affinity for insulin-like gr owth factor-II. The equilibrium binding affinities of a series of insulin-l ike growth factor-II mutants were also explained by differential dissociati on kinetics. O-glycosylation had a small effect on the association kinetics of insulin-like growth factor binding protein-6. The insulin-like growth f actor binding properties of insulin-like growth factor binding protein-6 ar e explained by differential dissociation kinetics. (C) 1999 Federation of E uropean Biochemical Societies.