Stöckl Martin, Fischer Patricia, Wanker Erich, Herrmann Andreas
Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, Institut für Biologie/Biophysik, Invalidenstr. 43, D-10115 Berlin, Germany.
J Mol Biol. 2008 Feb 1;375(5):1394-404. doi: 10.1016/j.jmb.2007.11.051. Epub 2007 Nov 22.
Previous studies indicate that binding of alpha-synuclein to membranes is critical for its physiological function and the development of Parkinson's disease (PD). Here, we have investigated the association of fluorescence-labeled alpha-synuclein variants with different types of giant unilamellar vesicles using confocal microscopy. We found that alpha-synuclein binds with high affinity to anionic phospholipids, when they are embedded in a liquid-disordered as opposed to a liquid-ordered environment. This indicates that not only electrostatic forces but also lipid packing and hydrophobic interactions are critical for the association of alpha-synuclein with membranes in vitro. When compared to wild-type alpha-synuclein, the disease-causing alpha-synuclein variant A30P bound less efficiently to anionic phospholipids, while the variant E46K showed enhanced binding. This suggests that the natural association of alpha-synuclein with membranes is altered in the inherited forms of Parkinson's disease.
先前的研究表明，α-突触核蛋白与膜的结合对其生理功能及帕金森病（PD）的发展至关重要。在此，我们使用共聚焦显微镜研究了荧光标记的α-突触核蛋白变体与不同类型的巨型单层囊泡之间的关联。我们发现，当阴离子磷脂嵌入液体无序而非液体有序环境中时，α-突触核蛋白以高亲和力与之结合。这表明，不仅静电力，而且脂质堆积和疏水相互作用对于α-突触核蛋白在体外与膜的关联也至关重要。与野生型α-突触核蛋白相比，致病的α-突触核蛋白变体A30P与阴离子磷脂的结合效率较低，而变体E46K则表现出增强的结合。这表明，在帕金森病的遗传形式中，α-突触核蛋白与膜的天然关联发生了改变。
