Apolipoprotein E isoprotein-specific interactions with tissue plasminogen activator.
Apolipoprotein E isoprotein-specific interactions with tissue plasminogen activator.
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DOI：
10.1016/j.bbadis.2004.04.004
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发表时间：
2004-08
期刊：
影响因子：
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通讯作者：
Susan J. Biehle;J. Carrozzella;R. Shukla;J. Popplewell;M. Swann;N. Freeman;Joseph F. Clark
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文献类型：
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作者：
Susan J. Biehle;J. Carrozzella;R. Shukla;J. Popplewell;M. Swann;N. Freeman;Joseph F. Clark
载脂蛋白E（Apo E）是多种神经、血管和心血管疾病的重要遗传危险因素。此前，我们使用体外凝血测定报告了组织纤溶酶原激活剂 (tPA) 的 Apo E 同蛋白特异性调节。在这里，我们使用圆二色性 (CD) 和双偏振干涉测量 (DPI) 研究了 tPA 存在下 Apo E2、E3 和 E4 的构象变化，反之亦然。我们报告了 Apo E 异构体和 tPA 之间的同种蛋白和状态特异性分子间相互作用。 Apo E2 与固定化 tPA 的相互作用会导致显着的构象变化，而 Apo E3 或 E4 则未观察到这一点。此外，tPA 会诱导脂化 Apo E2 的螺旋度发生变化，而在 Apo E3 或 E4 中未观察到可检测到的变化。 Tukey 相互作用检验表明，在脂化环境中，tPA 和 Apo E2 之间存在显着的相互作用（P<0.001）。这些结果可能对于 Apo E 对涉及凝血、蛋白水解和灌注的许多生物过程和疾病具有同蛋白特异性作用的机制很重要。
Apolipoprotein E (Apo E) is an important genetic risk factor for multiple neurological, vascular and cardiovascular diseases. Previously, we reported Apo E isoprotein-specific modulation of tissue plasminogen activator (tPA) using an in vitro blood-clotting assay. Here, we studied the conformational changes of Apo E2, E3 and E4 in the presence of tPA and vice versa using circular dichroism (CD) and dual polarization interferometry (DPI). We report isoprotein and state-specific intermolecular interactions between the Apo E isoforms and tPA. Apo E2 interaction with immobilized tPA leads to significant conformational changes which are not observed with Apo E3 or E4. Additionally, tPA induces changes in helicity of lipidated Apo E2 whereas no detectible changes were observed in Apo E3 or E4. The Tukey's test for interaction indicated a significant (P<0.001) interaction between tPA and Apo E2 in the lipidated environment. These results may be important regarding the mechanism by which Apo E has isoprotein-specific effects on many biological processes and diseases involving blood clotting, proteolysis and perfusion.