Camejo G, Rosengren B, Olson U, Lopez F, Olofson S O, Westerlund C, Bondjers G
Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sahlgren's Hospital, Sweden.
Eur Heart J. 1990 Aug;11 Suppl E:164-73. doi: 10.1093/eurheartj/11.suppl_e.164.
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.
进入动脉内膜的低密度脂蛋白（LDL）发生修饰，这似乎是其在动脉粥样硬化形成过程中最终在细胞外和细胞内蓄积的原因。其中一些修饰似乎是LDL与内膜富含硫酸软骨素的蛋白聚糖（CSPG）结合的结果。我们采用前沿洗脱亲和色谱法、与载脂蛋白B-100合成片段进行的结合及竞争实验，以更好地确定LDL-CSPG复合物的配体区域。CSPG识别的最小结构要求似乎是一个含有五个赖氨酸和精氨酸残基的亲水性九残基氨基酸片段。对载脂蛋白B-100和其他糖胺聚糖结合蛋白中其他类似区域的分析表明，除了一组带正电荷的氨基酸外，含羟基残基的存在有利于与硫酸化蛋白聚糖结合。通过可控的蛋白水解，我们发现LDL与CSPG的相互作用改变了载脂蛋白B-100中含精氨酸和赖氨酸片段的表面可及性。由于这些载脂蛋白B-100结构域可能也参与细胞受体结合，CSPG诱导的修饰可能是观察到的蛋白聚糖修饰的LDL细胞摄取增加的结构解释。
