Kinetics of apolipoprotein E isoforms-binding to the major glycosaminoglycans of the extracellular matrix

Apolipoprotein E (apoE), a key lipid transport protein, displays a heparin- binding property that is critical in several apoE functions. The kinetics o f the interaction between apoE isoforms and glycosaminoglycans (GAGs) were studied using surface plasmon resonance. The dissociation constant of equil ibrium KD for apoE3-heparin interaction was estimated to be 12 nM for apoE3 and three common apoE isoforms revealed similar affinities for heparin, Ap oE binds to GAGs in the following order: heparin > heparan sulfate > dermat an sulfate > chondroitin sulfate. The affinity parameter of the binding of low molecular weight heparins to apoE is correlated with the chain length. The effective number Z of electrostatic interactions between plasma apoE3 a nd heparin was assessed to be three. Metal chelators were able to diminish apoE-binding to heparin, suggesting some stabilizing effect of metal ions w hile reconstitution with lipids did not affect binding affinities for hepar in, suggesting that the N-terminal heparin-binding site is responsible for apoE-containing lipoprotein interactions with heparin, (C) 1999 Federation of European Biochemical Societies.