Membrane binding and self-association of α-synucleins
Membrane binding and self-association of α-synucleins
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DOI：
10.1021/bi002952n
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发表时间：
2001-08-21
期刊：
影响因子：
2.9
通讯作者：
Scarlata, S
中科院分区：
文献类型：
--
作者：
Narayanan, V;Scarlata, S
尽管其功能尚不清楚，但α-突触核蛋白广泛分布于神经组织中，并且是帕金森病、阿尔茨海默病、唐氏综合症和多系统萎缩症患者中发现的病理聚集体的主要成分。在本报告中，我们量化了 α-突触核蛋白与脂膜的结合。与之前的研究相反，我们发现，使用实时平衡荧光方法，α-突触核蛋白与具有阴离子或两性离子头基的大的单层囊泡牢固结合。 β-突触核蛋白、磷酸化 α-突触核蛋白以及与家族性帕金森病相关的突触核蛋白突变体的膜结合也很强。在低于 400 nM 的溶液中，突触核蛋白倾向于发生浓度依赖性寡聚化，这是由内在荧光和荧光共振能量转移的变化决定的。高于此浓度，蛋白质开始聚集成光散射可见的结构。虽然膜结合不影响α-突触核蛋白的二级结构，但它极大地抑制了该蛋白质的自缔合能力。综上所述，我们的结果表明病理状况可能与突触核蛋白-膜相互作用的破坏有关。
Although its function is unknown, alpha -synuclein is widely distributed in neural tissue and is the major component in the pathological aggregates found in patients with Parkinson's disease, Alzheimer's disease, Down's syndrome, and multiple system atrophy. In this report, we have quantified the binding alpha -synucleins to lipid membranes. In contrast to previous studies, we find, using real time equilibrium fluorescence methods, that alpha -synuclein binds strongly to large, unilamellar vesicles with either anionic or zwitterionic headgroups. Membrane binding is also strong for beta -synuclein, phosphorylated alpha -synuclein, and a synuclein mutant that is associated with familial Parkinson's disease. In solution at less than 400 nM, synuclein has a tendency to undergo concentration-dependent oligomerization as determined by changes in intrinsic fluorescence and fluorescence resonance energy transfer. Above this concentration, the protein begins to aggregate into structures visible by light scattering. Although membrane binding does not affect the secondary structure of alpha -synuclein, it greatly inhibits the ability of this protein to self-associate. Taken together, our results indicate that pathological conditions may be associated with a disruption in synuclein-membrane interactions.