Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement
Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement
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DOI：
10.1074/jbc.m210347200
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发表时间：
2003-01-31
影响因子：
4.8
通讯作者：
Kobayashi, T
中科院分区：
文献类型：
--
作者：
Makino, A;Baba, T;Kobayashi, T
肉桂霉素是一种独特的毒素，其受体磷脂酰乙醇胺(PE)位于质膜的内层。关于这种毒素是如何识别PE并引起细胞毒性的，人们知之甚少。我们发现，肉桂霉素诱导靶细胞中的跨双层磷脂运动，导致内叶PE暴露在毒素下。模型膜研究表明，肉桂霉素以一种浓度依赖的方式诱导跨双层脂质运动。磷脂的重新定位伴随着肉桂素中β-折叠结构的增加。当PE表面浓度较高时，肉桂霉素可引起膜的重组，如膜融合和膜的大体形态改变。这些结果表明，肉桂霉素促进其自身与细胞的结合，并通过诱导跨双层脂质运动而引起毒性。
Cinnamycin is a unique toxin in that its receptor, phosphatidylethanolamine (PE), resides in the inner layer of the plasma membrane. Little is known about how the toxin recognizes PE and causes cytotoxicity. We showed that cinnamycin induced transbilayer phospholipid movement in target cells that leads to the exposure of inner leaflet PE to the toxin. Model membrane studies revealed that cinnamycin induced transbilayer lipid movement in a PE concentration-dependent manner. Re-orientation of phospholipids was accompanied by an increase in the incidence of beta-sheet structure in cinnamycin. When the surface concentration of PE was high, cinnamycin induced membrane re-organization such as membrane fusion and the alteration of membrane gross morphology. These results suggest that cinnamycin promotes its own binding to the cell and causes toxicity by inducing transbilayer lipid movement.