Functional characterization of T7 and T8 of human apolipoprotein (a).

Functional characterization of T7 and T8 of human apolipoprotein (a).
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人载脂蛋白 T7 和 T8 的功能特征 (a)。

DOI:
10.1006/bbrc.1998.9478
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发表时间:
1998
期刊:
Biochemical and biophysical research communications.
影响因子:
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通讯作者:
McConathy,WJ
McConathy,WJ
中科院分区:
--
文献类型:
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作者:
Trieu,VN;McConathy,WJ

文献摘要

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脂蛋白(a)[Lp(a)]是一种脂蛋白样颗粒,其载脂蛋白(a)[apo(a)]与载脂蛋白B(apo B)共价连接,是冠心病的危险因子。载脂蛋白(a)具有许多kringle 4样结构域的重复序列,分为1型至10型(T1-T10)。进行缺失分析以确定人载脂蛋白(a)的功能模块。我们发现T7对细胞表面具有亲和力,并且是Lp(a)形成所需的。细胞表面结合受脯氨酸抑制,KI= 4.7 ± 3.6mM(n=3)。我们还发现T8对内皮下细胞外基质(ECM)具有亲和力。ECM结合受到脯氨酸(KI= 6.1 ± 1.9 mM,n=3)的适度抑制,赖氨酸(KI= 2.7 ± 1.0 mM,n=3)及其类似物6-氨基己酸(KI= 0.35 ± 0.13 mM,n=3)的抑制作用更强。这些数据表明T7和T8是apo(a)的重要功能模块。
Lipoprotein (a) [Lp(a)], a risk factor for coronary artery disease, is a LDL-like particle with apolipoprotein (a) [apo(a)] covalently linked to apolipoprotein B (apoB). Apo(a) has many repeats of kringle 4-like domain, classified as type 1 through type 10 (T1–T10). Deletion analysis was performed to define the functional modules of human apo(a). We found that T7 has an affinity for cell surfaces and is required for Lp(a) formation. Cell surface binding was inhibited byl-proline, KI= 4.7 ± 3.6 mM (n=3). We also found that T8 has an affinity for subendothelial extracellular matrix (ECM). ECM binding was inhibited modestly byl-proline (KI= 6.1 ± 1.9 mM, n=3), and more effectively byl-lysine (KI= 2.7 ± 1.0 mM, n=3) and its analogue, 6-aminohexanoic acid (KI= 0.35 ± 0.13 mM, n=3). These data point to T7 and T8 as important functional modules of apo(a).