title: Kinetics of apolipoprotein E isoforms-binding to the major glycosaminoglycans of the extracellular matrix.
abstract: Apolipoprotein E (apoE), a key lipid transport protein, displays a heparin-binding property that is critical in several apoE functions. The kinetics of the interaction between apoE isoforms and glycosaminoglycans (GAGs) were studied using surface plasmon resonance. The dissociation constant of equilibrium K(D) for apoE3-heparin interaction was estimated to be 12 nM for apoE3 and three common apoE isoforms revealed similar affinities for heparin. ApoE binds to GAGs in the following order: heparin>heparan sulfate>dermatan 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 and heparin was assessed to be three. Metal chelators were able to diminish apoE-binding to heparin, suggesting some stabilizing effect of metal ions while reconstitution with lipids did not affect binding affinities for heparin, suggesting that the N-terminal heparin-binding site is responsible for apoE-containing lipoprotein interactions with heparin.
authors.affiliation: Centre du Médicament, Université Henri Poincaré Nancy I, 30 rue Lionnois, 54000, Nancy, France.
authors.forename: V V
authors.initials: VV
authors.lastname: Shuvaev
authors.forename: I
authors.initials: I
authors.lastname: Laffont
authors.forename: G
authors.initials: G
authors.lastname: Siest
mesh_terms: D001057:Apolipoproteins E / Q000378:metabolism*; D001667:Binding, Competitive; D019921:Biotinylation; D002809:Chondroitin Sulfates / Q000378:metabolism; D003871:Dermatan Sulfate / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D020033:Protein Isoforms / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D001057:Apolipoproteins E; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D020033:Protein Isoforms