Binding of low density lipoproteins to lipoprotein lipase is dependent on lipids but not on apolipoprotein B.
Lipoprotein lipase (LPL) efficiently mediates the binding of lipoprotein particles to lipoprotein receptors and to proteoglycans at cell surfaces and in the extracellular matrix. It has been proposed that LPL increases the retention of atherogenic lipoproteins in the vessel wall and mediates the uptake of lipoproteins in cells, thereby promoting lipid accumulation and plaque formation. We investigated the interaction between LPL and low density lipoproteins (LDLs) with special reference to the protein-protein interaction between LPL and apolipoprotein B (apoB). Chemical modification of lysines and arginines in apoB or mutation of its main proteoglycan binding site did not abolish the interaction of LDL with LPL as shown by surface plasmon resonance (SPR) and by experiments with THP-I macrophages. Recombinant LDL with either apoB100 or apoB48 bound with similar affinity. In contrast, partial delipidation of LDL markedly decreased binding to LPL. In cell culture experiments, phosphatidylcholine-containing liposomes competed efficiently with LDL for binding to LPL. Each LDL particle bound several (up to 15) LPL dimers as determined by SPR and by experiments with THP-I macrophages. A recombinant NH(2)-terminal fragment of apoB (apoB17) bound with low affinity to LPL as shown by SPR, but this interaction was completely abolished by partial delipidation of apoB17. We conclude that the LPL-apoB interaction is not significant in bridging LDL to cell surfaces and matrix components; the main interaction is between LPL and the LDL lipids.
Boren
J
J
Wallenberg Laboratory, Göteborg University, S-41345 Göteborg, Sweden. jan.boren@wlab.wall.gu.se
Lookene
A
A
Makoveichuk
E
E
Xiang
S
S
Gustafsson
M
M
Liu
H
H
Talmud
P
P
Olivecrona
G
G
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D006493:Heparin / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008081:Liposomes; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D008081:Liposomes; D006493:Heparin; D008071:Lipoprotein Lipase