Inhibition of the binding of low-density lipoprotein to its cell surface receptor in human fibroblasts by positively charged proteins

A group of proteins and polyamino acids with positively charged domains were shown to inhibit the binding of ¹²⁵I-LDL to its receptor on the surface of human fibroblasts. The list of inhibitory proteins included platelet factor 4 (which has a cluster of lysine residues at its carboxyl terminus), two lysinerich histones, poly-L-lysines of chain length greater than 4, and protamine. These proteins were effective in the concentration range of 5–50 μg/ml. Two other positively charged proteins, lysozyme and avidin, did not inhibit ¹²⁵I-LDL binding. Kinetic studies suggested that protamine was not acting simply as a competitive inhibitor with regard to the LDL receptor. In light of previous data showing that polyanions such as heparin and polyphosphates also inhibit ¹²⁵I-LDL binding to its cell surface receptor, the current findings suggest that charge interactions are important in this binding reaction. In a related series of studies, a number of glycoproteins and their asialo derivatives as well as a number of sugar phosphates failed to inhibit ¹²⁵I-LDL binding to its receptor in fibroblasts.