Ca2+ binding to α-synuclein regulates ligand binding and oligomerization
Ca2+ binding to α-synuclein regulates ligand binding and oligomerization
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DOI：
10.1074/jbc.m101181200
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发表时间：
2001-06-22
影响因子：
4.8
通讯作者：
Jensen, PH
中科院分区：
文献类型：
--
作者：
Nielsen, MS;Vorum, H;Jensen, PH
α-突触核蛋白是一种通常参与突触前囊泡稳态的蛋白质。它参与帕金森病的发展，其中神经细胞病变，路易体，积累α-突触核蛋白丝。突触神经递质的释放主要依赖于 Ca2+ 调节过程。应用微透析技术显示α-突触核蛋白以约2-300μM的IC50结合Ca2+，并且在反应中不受50倍过量的Mg2+的抑制。 Ca2+ 结合位点由一个新的 C 端定位酸性 32 个氨基酸结构域组成，该结构域也存在于同源物 β-突触核蛋白中，如 Ca2+ 与截短的重组和合成 α-突触核蛋白肽的结合所示。 Ca2+ 结合影响 α-突触核蛋白的功能特性。首先，I-125 标记的牛微管相关蛋白 1A 的配体结合受到 1-500 muM 的 Ca2+ 离子的刺激。范围并依赖于 α-突触核蛋白中完整的 Ca2+ 结合位点。其次，Ca2+结合刺激了含有I-125-α-突触核蛋白寡聚体的比例，这表明Ca2+离子可能既参与神经末梢正常的α-突触核蛋白功能，又参与路易体形成中涉及的病理作用。
alpha -Synuclein is a protein normally involved in presynaptic vesicle homeostasis. It participates in the development of Parkinson's disease, in which the nerve cell lesions, Lewy bodies, accumulate alpha -synuclein filaments. The synaptic neurotransmitter release is primarily dependent on Ca2+-regulated processes. A microdialysis technique was applied showing that alpha -synuclein binds Ca2+ with an IC,, of about 2-300 muM and in a reaction uninhibited by a 50 fold excess of Mg2+. The Ca2+-binding site consists of a novel C-terminally localized acidic 32-amino acid domain also present in the homologue beta -synuclein, as shown by Ca2+ binding to truncated recombinant and synthetic alpha -synuclein peptides. Ca2+ binding affects the functional properties of alpha -synuclein, First, the ligand binding of I-125-labeled bovine microtubule-associated protein 1A is stimulated by Ca2+ ions in the 1-500 muM. range and is dependent on an intact Ca2+ binding site in alpha -synuclein. Second, the Ca2+ binding stimulates the proportion of I-125-alpha -synuclein-containing oligomers, This suggests that Ca2+ ions may both participate in normal alpha -synuclein functions in the nerve terminal and exercise pathological effects involved in the formation of Lewy bodies.