Alpha‐Synuclein Binds to the Inner Membrane of Mitochondria in an α‐Helical Conformation
Alpha‐Synuclein Binds to the Inner Membrane of Mitochondria in an α‐Helical Conformation
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DOI：
10.1002/cbic.201402281
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发表时间：
2014-11
期刊：
影响因子：
3.2
通讯作者：
M. Robotta;H. Gerding;Antonia Vogel;K. Hauser;S. Schildknecht;C. Karreman;M. Leist;V. Subramaniam;M. Drescher
中科院分区：
文献类型：
--
作者：
M. Robotta;H. Gerding;Antonia Vogel;K. Hauser;S. Schildknecht;C. Karreman;M. Leist;V. Subramaniam;M. Drescher
人α-突触核蛋白（αS）蛋白因其与帕金森病和相关神经退行性疾病的相关性而受到极大关注。本质上无序的蛋白质（140个氨基酸）的特征是在溶液中没有明确的结构。它在大分子相互作用时表现出显著的构象灵活性，并可与线粒体膜结合。定点自旋标记结合电子顺磁共振光谱使我们能够研究αS在人工膜（模拟线粒体内膜和外膜）上的局部结合特性，并评估心磷脂在这种相互作用中的重要性。利用脉冲双电子顺磁共振（DEER）方法，我们第一次尽我们所知检查了与分离线粒体结合的αS构象。
The human alpha‐Synuclein (αS) protein is of significant interest because of its association with Parkinson's disease and related neurodegenerative disorders. The intrinsically disordered protein (140 amino acids) is characterized by the absence of a well‐defined structure in solution. It displays remarkable conformational flexibility upon macromolecular interactions, and can associate with mitochondrial membranes. Site‐directed spin‐labeling in combination with electron paramagnetic resonance spectroscopy enabled us to study the local binding properties of αS on artificial membranes (mimicking the inner and outer mitochondrial membranes), and to evaluate the importance of cardiolipin in this interaction. With pulsed, twofrequency, double‐electron electron paramagnetic resonance (DEER) approaches, we examined, to the best of our knowledge for the first time, the conformation of αS bound to isolated mitochondria.