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 factor-II with a marked preferential affinity over insulin-like growth factor-I. The kinetic basis of this binding preference was studied using surface plasmon resonance. Binding of insulin-like growth factor-I and insulin-like growth 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 dissociation rate was approximately 60-fold lower for insulin-like growth factor-II, resulting in a higher equilibrium binding affinity for insulin-like growth factor-II. The equilibrium binding affinities of a series of insulin-like growth factor-II mutants were also explained by differential dissociation kinetics. O-glycosylation had a small effect on the association kinetics of insulin-like growth factor binding protein-6. The insulin-like growth factor binding properties of insulin-like growth factor binding protein-6 are explained by differential dissociation kinetics.
Marinaro
J A
JA
University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Vic, Australia.
Jamieson
G P
GP
Hogarth
P M
PM
Bach
L A
LA
D001667:Binding, Competitive; D002460:Cell Line; D006031:Glycosylation; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007700:Kinetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012996:Solutions; D020349:Surface Plasmon Resonance
D018976:Insulin-Like Growth Factor Binding Protein 6; D011993:Recombinant Fusion Proteins; D012996:Solutions; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II