The relationship between the effect of lysine analogues and salt on the conformation of lipoprotein(a).
The relationship between the effect of lysine analogues and salt on the conformation of lipoprotein(a).
复制标题
赖氨酸类似物和盐对脂蛋白(a)构象影响的关系。
作者：
Fless,GM;Halfman,CJ;Kirk,EW
脂蛋白(A)[Lp(A)]显示出许多与纤溶酶原相同的性质，这是因为由多个kringle结构域组成的化合物具有相似的结构组成。共同的行为包括由赖氨酸类似物诱导扩展的构象，抑制这一效应，以及由氯化钠创建紧凑的构象。在这里，我们详细研究了氯化钠和6-氨基己酸(6-AHA)对Lp(A)结构的独立和相互影响，以及两种配体之间的结合关系。我们发现，氯化钠促进了Lp(A)的致密构象，但与Lp(A)的结合是均匀的。在没有盐的情况下，6-AHA导致Lp(A)的完全解离，这一过程伴随着协同结合。当一种配体加入Lp(A)而另一种配体存在时，发生构象逆转和结合减弱，这表明竞争结合。高浓度的氯化钠完全逆转了Lp(A)在100 mM的6-AHA中的膨胀，高浓度的6-AHA在100 mM的氯化钠存在下使Lp(A)展开，但在所研究的15kringle IV Lp(A)的情况下仅增加了30%。Lp(A)致密形式的诱导似乎是所有被检查的盐的共同影响，不能像纤溶酶原那样完全归因于阴离子。结果用Lp(A)模型来描述两个配体结合引起的apo(A)的构象变化。在氯化钠中的致密构象中，apo(A)与颗粒表面相反。6-AHA中的完全展开形式是可变和恒定kringle结构域释放的结果。在水和同时含有氯化钠和6-AHA的溶液中的中间形式中，只有可变区从颗粒表面释放。
Lipoprotein(a) [Lp(a)] exhibits many of the same properties as plasminogen, owing to a similar structural makeup from a composite of multiple kringle domains. Shared behavior includes induction of an expanded conformation by lysine analogues, inhibition of this effect, and creation of a compact conformation by NaCl. Here, we examine in detail the independent and mutual effects of NaCl and 6-aminohexanoic acid (6-AHA) on the structure of Lp(a) and the relationship between the binding of the two ligands. We find that NaCl promotes the compact conformation while binding to Lp(a) homogeneously. In the absence of salt, 6-AHA leads to the complete unfolding of Lp(a), a process that is accompanied by cooperative binding. Reversal of conformation and weakening of binding occurred when one ligand was added to Lp(a) in the presence of the other, suggesting competitive binding. High concentrations of NaCl completely reversed the expansion of Lp(a) in 100 mM 6-AHA, and high concentrations of 6-AHA unfolded Lp(a) in the presence of 100 mM NaCl, but only by 30% in the case of the 15 kringle IV Lp(a) studied. Induction of the compact form of Lp(a) appears to be an effect in common with all salts examined and cannot be attributed solely to the anion, as in the case of plasminogen. The results were summarized in terms of a model of Lp(a) depicting the conformational alterations of apo(a) caused by the binding of the two ligands. In the compact conformation in NaCl, apo(a) is apposed to the particle surface. The fully expanded form in 6-AHA results from release of both the variable and constant kringle domains. In the intermediate form in water and in a solution containing both NaCl and 6-AHA, only the variable domain is released from the particle surface.