The apolipoprotein B3304-3317 peptide as an inhibitor of the lipoprotein (a):apolipoprotein B-containing lipoprotein interaction.
The apolipoprotein B3304-3317 peptide as an inhibitor of the lipoprotein (a):apolipoprotein B-containing lipoprotein interaction.
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载脂蛋白 B3304-3317 肽作为脂蛋白 (a):含载脂蛋白 B 的脂蛋白相互作用的抑制剂。
DOI：
10.1042/bj3070017
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
McConathy,WJ
中科院分区：
文献类型：
--
作者：
Trieu,VN;Olsson,U;McConathy,WJ
脂蛋白（a）[Lp（a）]是冠状动脉疾病的危险因素。其特征在于载脂蛋白（a）[apo（a）]二硫化物与载脂蛋白B（apo B）连接，apo（a）的Cys 4057和可能的apo B的Cys 3734。我们称之为共价apo（a）：apoB-Lp相互作用，以区别于由Lp（a）的脯氨酸结合kringle-4样结构域介导的非共价Lp（a）：apoB-Lp相互作用。Lp（a）：apoB-Lp相互作用被跨越残基3304-3317的apoB肽抑制。该肽是通过计算机搜索apoB上与α 2-抗纤溶酶的纤溶酶原kringle-4结合位点相似的位点而发现的。它可能构成apoB上Lp（a）-结合位点的一部分，因为：（1）它对应于纤溶酶原kringle-4的α 2-抗纤溶酶最小结合域;（2）抑制的竞争性[KI =（1.5 +/-0.7）× 10（-4）M，n = 5]表明它与apoB-Lp在同一位点以相同的机制结合Lp（a）;（3）它特异性结合Lp（a）而不结合apoB-Lp，结合的Lp（a）可被Lp（a）的抑制剂apoB-Lp相互作用、6-氨基己酸和L-脯氨酸解离。抑制作用与脯氨酸残基无关，表明脯氨酸在肽的背景下不是介导Lp（a）与apoB-Lp结合的kringle（s）的配体。
Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease. It is characterized by apolipoprotein (a) [apo(a)] disulphide linked to apolipoprotein B (apoB), by Cys4057 of apo(a) and possibly Cys3734 of apoB. We call this the covalent apo(a):apoB-Lp interaction, to distinguish it from the non-covalent Lp(a):apoB-Lp interaction, mediated by the proline-binding kringle-4-like domain(s) of Lp(a). The Lp(a):apoB-Lp interaction was inhibited by an apoB peptide spanning residues 3304-3317. This peptide was found by a computerized search for sites on apoB similar to the plasminogen's kringle-4-binding site of alpha 2-antiplasmin. It probably constitutes part of the Lp(a)-binding site on apoB because: (1) it corresponds to the alpha 2-antiplasmin minimum binding domain for plasminogen's kringle-4; (2) the competitive nature of inhibition [KI = (1.5 +/- 0.7) x 10(-4) M, n = 5] suggested that it and apoB-Lp bound to Lp(a) by the same mechanism at the same site; and (3) it specifically bound Lp(a) and not apoB-Lp, and the bound Lp(a) was dissociated by inhibitors of the Lp(a):apoB-Lp interaction, 6-aminohexanoic acid and L-proline. Inhibition was independent of its proline residue, suggesting that proline in the context of a peptide is not a ligand for the kringle(s) which mediated the binding of Lp(a) to apoB-Lp.