Cell surface receptor binding of phospholipid . protein complexes containing different ratios of receptor-active and -inactive E apoprotein.

Abstract

Previous data have shown that apo-E HDL, a lipoprotein containing only the E apoprotein, bind to fibroblast cell surface receptors with a higher affinity than do the apo-€3-containing low density lipoproteins (LDL).The enhanced affinity of apo-E NDL, results from multiple receptor binding (four receptors per HDL, particle).To study the molecular interaction of the E apoprotein with the lipoprotein receptors, apo-E was formed in a complex with dimyristoylphosphatidylcholine vesicles, and the equilibrium dissociation constants (&) for the binding of these complexes with the receptor were determined.In the dimyristoylphosphatidylcholine apoprotein complexes, the ratio of active apo-E, which was capable of receptor binding, to inactive apo-E, which was made incapable of receptor binding by acetoacetylation of the lysine residues, was varied.No differences were noted in the physicochemical properties of the complexes formed with either the active apo-E, inactive apo-E, or different ratios of the two.The complexes had a molecular weight of 760,000 and contained approximately 4 apo-E molecules/disk.Complexes which contained 4 active apo-E molecules bound with a & of 0.10 X IO-' M, a binding affinity similar to that of apo-E HDL, ( K d = 0.12 X lo-' M).Reduction in the number of active apo-E molecules per complex resulted in a reduction in binding affinity and an increase in the number of disks bound per cell.Complexes with 1 active and 3 inactive apo-E molecules/disk bound with an a…