Ca(2+) modulating α-synuclein membrane transient interactions revealed by solution NMR spectroscopy.
Ca(2+) modulating α-synuclein membrane transient interactions revealed by solution NMR spectroscopy.
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DOI：
10.1016/j.bbamem.2013.11.016
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发表时间：
2014-03
期刊：
影响因子：
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通讯作者：
Zeting Zhang;Chenye Dai;Jia Bai;Guohua Xu;Maili Liu;Conggang Li
中科院分区：
文献类型：
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作者：
Zeting Zhang;Chenye Dai;Jia Bai;Guohua Xu;Maili Liu;Conggang Li
α-突触核蛋白参与了帕金森病的发病过程，其与细胞膜的相互作用对其病理生理功能至关重要。膜的性质，如曲率和脂质成分，已被证明会影响相互作用的各种技术，但离子对α-突触核蛋白膜相互作用的影响仍然难以捉摸。神经元内Ca ~（2+）的动态波动在帕金森病的发病中起重要作用，Ca ~（2+）内流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，在这里，我们表明，Ca 2+可以调节α-突触核蛋白膜的相互作用，通过竞争性结合到阴离子脂质，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性调节作用，这可能为神经退行性疾病中的功能障碍提供线索。
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. Ca2 +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 Ca2 +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 Ca2 +on membrane mediated normal function of α-synuclein, which may provide a clue, to their dysfunction in neurodegenerative disease.