Cheng Q, Blackett P, Jackson K W, McConathy W J, Wang C S
Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City.
Biochem J. 1990 Jul 15;269(2):403-7. doi: 10.1042/bj2690403.
In this study we have prepared peptides of the C-terminal domain of apolipoprotein CII (ApoCII) by a solid-peptide-synthesis technique and demonstrated that the C-terminal tetrapeptide, Lys-Gly-Glu-Glu, represents an inhibitor of lipoprotein lipase. The tetrapeptide not only inhibits the basal activity of lipoprotein lipase, but also blocks the activation effect of native ApoCII. The lengthening of this tetrapeptide resulted in a corresponding increase in affinity for lipoprotein lipase. This suggested that amino acids other than those of the C-terminal tetrapeptide also contribute to the binding affinity of ApoCII for lipoprotein lipase. On the basis of an essential requirement of the ApoCII terminal domain for binding to lipoprotein lipase, we suggest that the initial interaction of ApoCII, mediated via the C-terminal tetrapeptide, promotes the proper alignment of ApoCII with lipoprotein lipase, followed by the weak interaction of the ApoCII activator domain with the lipoprotein lipase activator site, enhancing the lipolysis process.
在本研究中，我们通过固相肽合成技术制备了载脂蛋白CII（ApoCII）C末端结构域的肽段，并证明C末端四肽Lys-Gly-Glu-Glu是脂蛋白脂肪酶的抑制剂。该四肽不仅抑制脂蛋白脂肪酶的基础活性，还阻断天然ApoCII的激活作用。该四肽的延长导致其对脂蛋白脂肪酶的亲和力相应增加。这表明除C末端四肽的氨基酸外，其他氨基酸也对ApoCII与脂蛋白脂肪酶的结合亲和力有贡献。基于ApoCII末端结构域与脂蛋白脂肪酶结合的基本要求，我们认为ApoCII通过C末端四肽介导的初始相互作用促进了ApoCII与脂蛋白脂肪酶的正确排列，随后ApoCII激活结构域与脂蛋白脂肪酶激活位点发生弱相互作用，增强了脂解过程。
