title: Lipoprotein lipase association with lipoproteins involves protein-protein interaction with apolipoprotein B.
abstract: Lipoprotein lipase (LPL) hydrolyzes chylomicron and very low density lipoprotein (VLDL) triglycerides and potentiates the cellular uptake of lipoproteins. These LPL-lipoprotein associations could involve only protein-lipid interaction, or they could be modulated by apolipoproteins (apo). ApoB is the major protein component of chylomicrons, VLDL, and low density lipoprotein (LDL). ApoB100, a large glycoprotein with a molecular mass of 550 kDa, is composed of several functional domains. A carboxyl-terminal region of the protein is the ligand for the LDL receptor. There are several hydrophobic domains that are believed to be important in lipid binding. The relatively hydrophilic amino-terminal region of apoB, however, has no known function. Using solid phase assays we quantified LPL-lipoprotein complex formation. On a molar basis, severalfold greater amounts of LPL bound to LDL and VLDL than to high density lipoprotein at all the concentrations of LPL tested (0.9-55 nM). To assess the roles of LDL protein versus lipid, we performed competition and ligand blotting experiments. LDL and an amino-terminal fragment of apoB competed better for 125I-LPL binding to LDL than did lipid emulsion particles. Delipidation of LDL-coated plates did not alter LPL binding. On ligand blots, LPL bound to amino-terminal fragments of apoB generated by thrombin digestion but not to apoA1, apoE, or carboxyl-terminal fragments of apoB. Further evidence for LPL interaction with the amino-terminal region of apoB was obtained using anti-apoB monoclonal antibodies. Antibodies directed against the amino-terminal regions of apoB blocked LPL interaction with LDL, whereas those against the carboxyl-terminal region of apoB did not inhibit LPL interaction with LDL. Thus, we conclude that a specific interaction between LPL and the amino-terminal region of apoB may facilitate LPL association with circulating lipoproteins.
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Choi
authors.forename: P
authors.initials: P
authors.lastname: Sivaram
authors.forename: D E
authors.initials: DE
authors.lastname: Walker
authors.forename: L K
authors.initials: LK
authors.lastname: Curtiss
authors.forename: D G
authors.initials: DG
authors.lastname: Gretch
authors.forename: S L
authors.initials: SL
authors.lastname: Sturley
authors.forename: A D
authors.initials: AD
authors.lastname: Attie
authors.forename: R J
authors.initials: RJ
authors.lastname: Deckelbaum
authors.forename: I J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001055:Apolipoproteins B / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B; D008074:Lipoproteins; D008071:Lipoprotein Lipase