Phosphatidylethanolamine enhances amyloid fiber-dependent membrane fragmentation.
Phosphatidylethanolamine enhances amyloid fiber-dependent membrane fragmentation.
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DOI：
10.1021/bi3009888
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发表时间：
2012-10-02
期刊：
影响因子：
2.9
通讯作者：
Ramamoorthy A
中科院分区：
文献类型：
--
作者：
Sciacca MF;Brender JR;Lee DK;Ramamoorthy A
假设淀粉样蛋白形成肽的毒性驻留在蛋白质低聚物与细胞膜相互作用和破坏细胞膜相互作用的能力上。该假设的许多证据来自使用模型膜的体外实验。但是，这种方法的准确性取决于模型膜准确模拟细胞膜的能力。在模型系统中淀粉样蛋白毒性的许多研究中，膜组成的作用被忽略了。通过结合膜结合，膜通透性和纤维形成的测量，我们表明脂质与磷脂酰乙醇胺（PE）头组相结合，强烈调节IAPP诱导的膜破坏（胰岛多肽蛋白质），一种淀粉样蛋白酶蛋白质的蛋白质II II诊断。我们的结果表明，PE脂质阻碍了纤维纤维IAPP与膜的相互作用，但增强了通过清洁剂样机制与膜表面上的纤维生长相关的膜破坏。这些发现提供了对IAPP诱导的膜破坏机制的见解，这表明PE也可能对参与其他病理学的其他淀粉样蛋白起作用。
The toxicity of amyloid-forming peptides has been hypothesized to reside in the ability of protein oligomers to interact with and disrupt the cell membrane. Much of the evidence for this hypothesis comes from in vitro experiments using model membranes. However, the accuracy of this approach depends on the ability of the model membrane to accurately mimic the cell membrane. The effect of membrane composition has been overlooked in many studies of amyloid toxicity in model systems. By combining measurements of membrane binding, membrane permeabilization, and fiber formation, we show that lipids with the phosphatidylethanolamine (PE) head group strongly modulate the membrane disruption induced by IAPP (islet amyloid polypeptide protein), an amyloidogenic protein involved in type II diabetes. Our results suggest that PE lipids hamper the interaction of prefibrillar IAPP with membranes, but enhance the membrane disruption correlated with the fiber growth on the membrane surface via a detergent-like mechanism. These findings provide insights into the mechanism of membrane disruption induced by IAPP, suggesting a possible role of PE also for other amyloids involved in other pathologies.
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