Segments in the C-terminal Folding Domain of Lipoprotein Lipase Important for Binding to the Low Density Lipoprotein Receptor-related Protein and to Heparan Sulfate Proteoglycans*

Lipoprotein lipase (LpL) can mediate cellular uptake of chylomicron and VLDL remnants via binding to heparan sulfate proteoglycans (HSPG) and the endocytic α2-macroglobulin receptor/low density lipoprotein receptor-related protein (α2MR/LRP). Whereas it is established that the C-terminal folding domain binds to α2MR/LRP, it remains uncertain whether it binds to heparin and to HSPG. To identify segments important for binding to α2MR/LRP and to clarify possible binding to heparin, we produced constructs of the human C-terminal folding domain, LpL-(313-448), and of the fragment LpL-(347-448) in Escherichia coli. In addition to binding to α2MR/LRP, LpL-(313-448) displayed binding to heparin with an affinity similar to that of the LpL monomer, whereas it bound poorly to lipoprotein particles. Moreover, LpL-(313-448) displayed heparin sensitive binding to normal, but not to HSPG deficient Chinese hamster ovary cells. LpL-(313-448) and LpL-(347-448) showed similar affinities for binding to both purified α2MR/LRP and to heparin. Deletion of LpL residues 380-384 abolished the binding to LRP, whereas binding to heparin was unperturbed. The binding to both heparin and α2MR/LRP was essentially abolished following deletion of residues 404-430, and pretreatment of CHO cells with the peptide comprising aa 402-423 inhibited the binding of LpL-(313-448). We conclude that the C-terminal folding domain of human LpL has a site for binding to heparin and to HSPG, presumably involving amino acids within residues 404-430. Two segments of the domain are necessary for efficient binding to α2MR/LRP, one comprising residues 380-384 and another overlapping the segment important for binding to heparin.

• Publication year

  1997

• Venue

  Journal of Biological Chemistry

• Publication date

  1997-02-28

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.272.9.5821PMID 9038197
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Heparin Structure and Interactions with Basic Fibroblast Growth Factor

  1996cited by this paper
• Hepatic lipase mediates the uptake of chylomicrons and beta-VLDL into cells via the LDL receptor-related protein (LRP).

  1996cited by this paper
• Vimentin filaments follow the preexisting cytokeratin network during epithelial-mesenchymal transition of cultured neonatal rat hepatocytes.

  1996cited by this paper
• Analysis of ligand binding to the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Evidence that lipoprotein lipase and the carboxyl-terminal domain of the receptor-associated protein bind to the same site.

  1995cited by this paper
• Human Hepatic and Lipoprotein Lipase: The Loop Covering the Catalytic Site Mediates Lipase Substrate Specificity (*)

  1995cited by this paper
• Enhancement of the Binding of Triglyceride-rich Lipoproteins to the Very Low Density Lipoprotein Receptor by Apolipoprotein E and Lipoprotein Lipase (*)

  1995cited by this paper
• Actin cytoskeleton of fibroblasts organizes surface proteoglycans that bind basic fibroblast growth factor and lipoprotein lipase.

  1995cited by this paper
• Structure of heparin fragments with high affinity for lipoprotein lipase and inhibition of lipoprotein lipase binding to alpha 2-macroglobulin-receptor/low-density-lipoprotein-receptor-related protein by heparin fragments.

  1995cited by this paper
• The Cellular Internalization and Degradation of Hepatic Lipase Is Mediated by Low Density Lipoprotein Receptor-related Protein and Requires Cell Surface Proteoglycans (*)

  1995cited by this paper
• Structural features in lipoprotein lipase necessary for the mediation of lipoprotein uptake into cells.

  1995cited by this paper
• Lipoprotein lipase mass and activity in plasma and their increase after heparin are separate parameters with different relations to plasma lipoproteins.

  1995cited by this paper
• Three-dimensional structure of the second cysteine-rich repeat from the human low-density lipoprotein receptor.

  1995cited by this paper
• Heparan Sulfate Proteoglycans Are Primarily Responsible for the Maintenance of Enzyme Activity, Binding, and Degradation of Lipoprotein Lipase in Chinese Hamster Ovary Cells (*)

  1995cited by this paper
• Functional expression of low density lipoprotein receptor-related protein is controlled by receptor-associated protein in vivo.

  1995cited by this paper
• Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein and scavenger receptor in human atherosclerotic lesions.

  1994cited by this paper
• Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP).

  1994cited by this paper
• The carboxyl-terminal domain of lipoprotein lipase binds to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) and mediates binding of normal very low density lipoproteins to LRP.

  1994cited by this paper
• The alpha 2-macroglobulin receptor and epithelial glycoprotein-330: two giant receptors mediating endocytosis of multiple ligands.

  1994cited by this paper
• A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoprotein in cells.

  1994cited by this paper
• Structure, function and role of lipoprotein lipase in lipoprotein metabolism.

  1994cited by this paper
• Molecular dissection of ligand binding sites on the low density lipoprotein receptor-related protein.

  1994cited by this paper
• Lipoprotein lipase. Molecular model based on the pancreatic lipase x-ray structure: consequences for heparin binding and catalysis.

  1994cited by this paper
• Mutagenesis in four candidate heparin binding regions (residues 279-282, 291-304, 390-393, and 439-448) and identification of residues affecting heparin binding of human lipoprotein lipase.

  1994cited by this paper
• Functional characterization of a chimeric lipase genetically engineered from human lipoprotein lipase and human hepatic lipase.

  1993cited by this paper
• Binding of lipoprotein lipase to heparin. Identification of five critical residues in two distinct segments of the amino-terminal domain.

  1993cited by this paper
• Absence of triglyceride accumulation in lipoprotein lipase-deficient human monocyte-macrophages incubated with human very low density lipoprotein.

  1993cited by this paper
• Chymotryptic cleavage of lipoprotein lipase. Identification of cleavage sites and functional studies of the truncated molecule.

  1993cited by this paper
• Glycoprotein 330, a member of the low density lipoprotein receptor family, binds lipoprotein lipase in vitro.

  1993cited by this paper
• Alpha 2-macroglobulin-proteinase complexes, plasminogen activator inhibitor type-1-plasminogen activator complexes, and receptor-associated protein bind to a region of the alpha 2-macroglobulin receptor containing a cluster of eight complement-type repeats.

  1993cited by this paper
• The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase.

  1993cited by this paper
• Lipoprotein lipase induces catabolism of normal triglyceride-rich lipoproteins via the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in vitro. A process facilitated by cell-surface proteoglycans.

  1993cited by this paper
• Mapping of the epitope on lipoprotein lipase recognized by a monoclonal antibody (5D2) which inhibits lipase activity.

  1992cited by this paper
• Chimeras of hepatic lipase and lipoprotein lipase. Domain localization of enzyme-specific properties.

  1992cited by this paper
• Analysis of ligand recognition by the purified alpha 2-macroglobulin receptor (low density lipoprotein receptor-related protein). Evidence that high affinity of alpha 2-macroglobulin-proteinase complex is achieved by binding to adjacent receptors.

  1991cited by this paper
• Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein.

  1991cited by this paper
• Phospholipase activity of milk lipoprotein lipase.

  1991cited by this paper
• Structure of human pancreatic lipase

  1990cited by this paper
• Tumor formation dependent on proteoglycan biosynthesis.

  1988cited by this paper
• Studies on inactivation of lipoprotein lipase: role of the dimer to monomer dissociation.

  1985cited by this paper

• Evinacumab Improved the Homozygous Familial Hypercholesterolemia Lipid Metabolism: A Case Report.

  2025cites this paper
• Two Novel Mutations Associated with Familial Chylomicronemia in a Neonate

  2024cites this paper
• Macromolecular Interactions of Lipoprotein Lipase (LPL).

  2024cites this paper
• Heparan Sulfate: A Regulator of White Adipocyte Differentiation and of Vascular/Adipocyte Interactions

  2022cites this paper
• The Importance of Lipoprotein Lipase Regulation in Atherosclerosis

  2021cites this paper
• Two peptides targeting endothelial receptors are internalized into murine brain endothelial cells

  2021cites this paper
• Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity[S]

  2018cites this paper
• Biochemical Analysis of the LPL Truncation Variant, LPL S447X Reveals Increased Lipoprotein Uptake

  2018cites this paper
• We FRET so You Don't Have To: New Models of the Lipoprotein Lipase Dimer.

  2018cites this paper
• 1 Insulin Secretion and Actions

  2017cites this paper
• Biochemical Analysis of the Lipoprotein Lipase Truncation Variant, LPLS447X, Reveals Increased Lipoprotein Uptake.

  2017cites this paper
• Implicación del Low Density Lipoprotein Receptor-Related Protein 1 (LRP1) en el remodelado vascular y cardiaco

  2015cites this paper
• Cardiomyocyte intracellular cholesteryl ester accumulation promotes tropoelastin physical alteration and degradation: Role of LRP1 and cathepsin S.

  2014cites this paper
• [New insights in regulation factors of lipoprotein lipase].

  2013influential citation
• Glycosylphosphatidylinositol‐anchored high‐density lipoprotein‐binding protein 1 and the intravascular processing of triglyceride‐rich lipoproteins

  2012cites this paper
• Insulin Secretion and Actions

  2011cites this paper
• The concentration of extracellular superoxide dismutase in plasma is maintained by LRP-mediated endocytosis.

  2010cites this paper
• LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies.

  2008cites this paper
• Role of adipocyte-derived lipoprotein lipase in adipocyte hypertrophy

  2007cites this paper
• Isolation and Characterization of Low Sulfated Heparan Sulfate Sequences with Affinity for Lipoprotein Lipase*

  2006cites this paper
• Lipoprotein Lipase S447X: A Naturally Occurring Gain-of-Function Mutation

  2006cites this paper
• Acute intralipid infusion reduces cardiac luminal lipoprotein lipase but recruits additional enzyme from cardiomyocytes.

  2006cites this paper
• Inhibition of Glycosaminoglycan Synthesis Using Rhodamine B in a Mouse Model of Mucopolysaccharidosis Type IIIA

  2006cites this paper
• Lipoprotein lipase S447X : from benefical gene variant to gene therapy

  2006cites this paper
• 7 lipoprotein lipase Gene polymorphisms and the risk of tarGet vessel revascularization after percutaneous coronary intervention

  2006cites this paper
• The cardiovascular metabolic syndrome

  2005cites this paper
• Regulation of macrophage lipoprotein lipase gene expression by interferon-gamma

  2005cites this paper
• Lipoprotein lipase gene polymorphisms and the risk of target vessel revascularization after percutaneous coronary intervention.

  2005cites this paper
• Structural basis of endothelial lipase tropism for HDL

  2004cites this paper
• Lipoprotein lipase in hemodialysis patients and healthy controls : effects of heparin

  2004cites this paper
• Lipids in Health and Disease

  2004influential citation
• Altered Substrate Utilization in the Diabetic Heart: Role of Lipoprotein Lipase

  2003cites this paper
• Low density lipoprotein receptor-related protein (LRP) is a heparin-dependent adhesion receptor for connective tissue growth factor (CTGF) in rat activated hepatic stellate cells.

  2003cites this paper
• Differential binding of platelet-derived growth factor isoforms to glycosaminoglycans

  2003influential citation
• LIP ASES IN MILK

  2003cites this paper
• Lipases in Milk

  2003cites this paper
• The sequence, expression, and chromosomal localization of a novel polycystic kidney disease 1-like gene, PKD1L1, in human.

  2002cites this paper
• In situ heparin‐induced peroxisomal reticulum and biogenesis of peroxisomes in pulmonary intravascular macrophages (PIMs) of caprine lung: an ultrastructural and cytochemical study

  2002cites this paper
• Molecular modeling of the dimeric structure of human lipoprotein lipase and functional studies of the carboxyl-terminal domain.

  2002cites this paper
• Lipoprotein lipase: structure, function, regulation, and role in disease

  2002cites this paper
• Heparin-binding defective lipoprotein lipase is unstable and causes abnormalities in lipid delivery to tissues.

  2001cites this paper
• Ultrastructural response of pulmonary intravascular macrophages to exogenous oestrogen in the bovine lung: translocation of the surface‐coat and enhanced cell membrane plasticity and angiogenesis

  2001cites this paper
• Endothelial chylomicron binding is altered by interaction with high-density lipoprotein in Heymann's nephritis.

  2001cites this paper
• Contribution of the carboxy-terminal domain of lipoprotein lipase to interaction with heparin and lipoproteins.

  2000cites this paper
• Lipoprotein lipase (C/G)447 polymorphism and blood pressure in the Stanislas Cohort

  2000cites this paper
• High Affinity Binding between Lipoprotein Lipase and Lipoproteins Involves Multiple Ionic and Hydrophobic Interactions, Does Not Require Enzyme Activity, and Is Modulated by Glycosaminoglycans*

  2000cites this paper
• The release of lipoprotein lipase from 3T3-L1 adipocytes is regulated by microvessel endothelial cells in an insulin-dependent manner.

  2000cites this paper
• Functions of cell surface heparan sulfate proteoglycans.

  1999cites this paper
• Sortilin/Neurotensin Receptor-3 Binds and Mediates Degradation of Lipoprotein Lipase*

  1999cites this paper
• Oxidative modification of apolipoprotein E in human very-low-density lipoprotein and its inhibition by glycosaminoglycans.

  1999cites this paper
• Regulation of cardiac lipoprotein lipase during hypertension and diabetes

  1999cites this paper
• The mammalian low-density lipoprotein receptor family.

  1999cites this paper
• Analysis of a Structural Determinant in Thrombin-Protease Nexin 1 Complexes That Mediates Clearance by the Low Density Lipoprotein Receptor-related Protein*

  1999cites this paper
• Heparin-Binding Proteins in Lipoprotein Metabolism

  1998cites this paper
• Receptors of the low density lipoprotein (LDL) receptor family in man. Multiple functions of the large family members via interaction with complex ligands.

  1998cites this paper
• Subdomain Chimeras of Hepatic Lipase and Lipoprotein Lipase

  1998cites this paper
• Ligand-receptor interactions of the low density lipoprotein receptor-related protein, a multi-ligand endocytic receptor

  1998cites this paper
• Binding of urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex to the endocytosis receptors alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein and very-low-density lipoprotein receptor involves basic residues in the inhibitor.

  1998cites this paper
• Detailed characterization of the binding site of the lipoprotein lipase-specific monoclonal antibody 5D2.

  1998cites this paper
• Binding and intracellular trafficking of lipoprotein lipase and triacylglycerol-rich lipoproteins by liver cells.

  1998cites this paper
• The carboxy-terminal region of human lipoprotein lipase is necessary for its exit from the endoplasmic reticulum.

  1998cites this paper
• Heparan sulfate proteoglycans of the cardiovascular system. Specific structures emerge but how is synthesis regulated?

  1997cites this paper
• Perspectives Series: Cell Adhesion in Vascular Biology

  1997cites this paper
• Heparan sulfate proteoglycans of the cardiovascular system. Specific structures emerge but how is synthesis regulated?

  1997cites this paper
• The Efficient Catabolism of Thrombin-Protease Nexin 1 Complexes Is a Synergistic Mechanism That Requires Both the LDL Receptor-related Protein and Cell Surface Heparins*

  1997cites this paper
• Ldl Receptor-related Protein 1: Unique Tissue-specific Functions Revealed by Selective Gene Knockout Studies

  year unknowncites this paper