Zhang Zeting, Dai Chenye, Bai Jia, Xu Guohua, Liu Maili, Li Conggang
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China.
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China; Graduate University of Chinese Academy of Sciences, Beijing 100029, PR China.
Biochim Biophys Acta. 2014 Mar;1838(3):853-8. doi: 10.1016/j.bbamem.2013.11.016. Epub 2013 Dec 4.
α-Synuclein is involved in Parkinson's disease and its interaction with cell membrane is crucial to its pathological and physiological functions. Membrane properties, such as curvature and lipid composition, have been shown to affect the interactions by various techniques, but ion effects on α-synuclein membrane interactions remain elusive. Ca(2+) dynamic fluctuation in neurons plays important roles in the onset of Parkinson's disease and its influx is considered as one of the reasons to cause cell death. Using solution Nuclear Magnetic Resonance (NMR) spectroscopy, here we show that Ca(2+) can modulate α-synuclein membrane interactions through competitive binding to anionic lipids, resulting in dissociation of α-synuclein from membranes. These results suggest a negative modulatory effect of Ca(2+) on membrane mediated normal function of α-synuclein, which may provide a clue, to their dysfunction in neurodegenerative disease.
α-突触核蛋白与帕金森病有关，其与细胞膜的相互作用对其病理和生理功能至关重要。膜的性质，如曲率和脂质组成，已通过各种技术表明会影响这种相互作用，但离子对α-突触核蛋白膜相互作用的影响仍不清楚。神经元中Ca(2+)的动态波动在帕金森病的发病中起重要作用，其流入被认为是导致细胞死亡的原因之一。利用溶液核磁共振（NMR）光谱技术，我们在此表明Ca(2+)可通过与阴离子脂质竞争结合来调节α-突触核蛋白与膜的相互作用，导致α-突触核蛋白从膜上解离。这些结果表明Ca(2+)对α-突触核蛋白膜介导的正常功能具有负调节作用，这可能为其在神经退行性疾病中的功能障碍提供线索。
