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 lysine-rich histones, poly-L-lysines of chain length greater than 4, and protamine. These proteins were effective in the concentration range of 5--10 microgram/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 125-I-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.
D001779:Blood Coagulation Factors / Q000378:metabolism*; D002460:Cell Line; D002788:Cholesterol Esters / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D007526:Isoelectric Point; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010978:Platelet Factor 4 / Q000378:metabolism*; D011107:Polylysine / Q000378:metabolism; D011479:Protamines / Q000378:metabolism; D011485:Protein Binding; D011955:Receptors, Drug / Q000378:metabolism*
D001779:Blood Coagulation Factors; D002788:Cholesterol Esters; D006657:Histones; D008077:Lipoproteins, LDL; D011479:Protamines; D011955:Receptors, Drug; D011107:Polylysine; D010978:Platelet Factor 4