title: Molecular basis of the association of arterial proteoglycans with low density lipoproteins: its effect on the structure of the lipoprotein particle.
abstract: Modifications of low density lipoproteins (LDL) that enter the arterial intima appear to be responsible for their eventual extracellular and intracellular accumulation during atherogenesis. Some of these modifications seem to be the result of LDL association with intimal chondroitin sulphate-rich proteoglycans (CSPG). We have used frontal elution affinity chromatography, binding and competition experiments with synthetic segments of apoB-100 to better define the ligand regions for the LDL-CSPG complexes. The minimum structural requirement for recognition by the CSPG appears to be a hydrophilic nine-residue amino-acid segment with five lysine and arginine residues. Analysis of other similar regions in apoB-100 and other glycosaminoglycan-binding proteins suggest that besides a cluster of positively charged amino-acids, the presence of hydroxyl-containing residues favours the association with sulphated proteoglycans. With controlled proteolytic hydrolysis, we found that the interaction of LDL with CSPG modifies the surface accessibility of a apoB-100 segments containing arginine and lysine. Because these apoB-100 domains may also be involved in cell-receptor binding, the CSPG-induced modifications could be the structural explanation for the observed increase in cellular uptake of proteoglycan-modified LDL.
authors.affiliation: Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sahlgren's Hospital, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Camejo
authors.forename: B
authors.initials: B
authors.lastname: Rosengren
authors.forename: U
authors.initials: U
authors.lastname: Olson
authors.forename: F
authors.initials: F
authors.lastname: Lopez
authors.forename: S O
authors.initials: SO
authors.lastname: Olofson
authors.forename: C
authors.initials: C
authors.lastname: Westerlund
authors.forename: G
authors.initials: G
authors.lastname: Bondjers
mesh_terms: D000595:Amino Acid Sequence; D001011:Aorta / Q000737:chemistry; D002846:Chromatography, Affinity; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000737:chemistry*
chemical_list: D008077:Lipoproteins, LDL; D011509:Proteoglycans