INTERACTION OF PLASMA-LIPOPROTEINS CONTAINING APOLIPOPROTEIN-B AND APOLIPOPROTEIN-E WITH HEPARIN AND CELL-SURFACE RECEPTORS

Low density lipoproteins (LDL) containing apolipoprotein B and a high density lipoprotein (the HDLc) containing apolipoprotein E bind to the same cell surface receptors of fibroblasts and also bind to and are precipitated by heparin. To determine if the nature of the chemical interaction of these lipoproteins with the receptor and with heparin were identical, we undertook to compare the effects of the chemical modification of selected amino acid residues of these lipoproteins on receptor and heparin binding activities. Previously, we reported the importance of the positively charged amino acids arginine and lysine in the interaction of LDL and HDLc with the cell surface receptors. Lysine residues were modified by a procedure which did not alter the positive charge on the ε{lunate}-amino group (reductive methylation) or by procedures which neutralized this positive charge (acetoacetylation and carbamylation). Modification of arginyl residues was accomplished using 1,2-cyclohexanedione. Whereas all procedures used to modify the arginine and lysine residues totally abolished receptor binding activity, only the procedures which neutralized the positive charge of these residues abolished heparin binding. Reductive methylation of the lysine residues, which preserved the positive charge on the ε{lunate}-amino group, did not significantly prevent heparin binding or heparin precipitation of LDL or HDLc. Several conclusions are possible from the results of these studies. The protein moieties of both the LDL (apolipoprotein B) and HDLc (apolipoprotein E) can interact with heparin. Furthermore, both arginine and lysine residues participate in the interaction of these lipoproteins with heparin,apparently through an ionic interaction between the positively charged guanido group of arginine or the ε{lunate}-amino group of lysine and the heparin. Although the same residues (arginine and lysine) are involved in cell surface receptor binding of these lipoproteins, the nature of the chemical interaction appears to be different and does not appear to be strictly ionic. © 1979.