Metal binding to alpha-synuclein peptides and its contribution to toxicity
Metal binding to alpha-synuclein peptides and its contribution to toxicity
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DOI：
10.1016/j.bbrc.2009.01.103
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发表时间：
2009-03-06
影响因子：
3.1
通讯作者：
Brown, David R.
中科院分区：
文献类型：
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作者：
Brown, David R.
最近的研究表明，α -突触核蛋白（AS）是一种金属结合蛋白。金属也能诱导蛋白质聚集。为了澄清关于金属结合位点位置的争议，分析了跨越蛋白质全长的六个肽片段以确定金属结合域。我们的研究结果表明，蛋白质的c端和组氨酸50周围的区域都在铜结合中起作用。我们认为真正的结合域是一个非线性位点，由两个区域共同作用来结合铜。我们还研究了这些肽对SH-SY5Y细胞的毒性。有一个与蛋白质的NAC结构域相关的不依赖铜的组分和一个与蛋白质的c端相关的依赖铜的组分，并通过参与n端而增强。我们假设铜结合call通过蛋白间相互作用导致AS转化为神经毒性形式。(C) 2009爱思唯尔公司版权所有
Recent studies have Suggested that alpha-synuclein (AS) is a metal binding protein. Metals also induce protein aggregation. In order to clarify controversy over the location of the metal binding sites six peptide fragments spanning the full length of the protein were analysed to identify metal binding domains. Our results indicated that both the C-terminus of the protein and a region around histidine 50 play a role ill copper binding. We suggest that the true binding domain is a nonlinear site composed of both areas acting together to bind copper. The toxicity of these peptides to SH-SY5Y cells was also Studied. There was a copper-independent component associated with the NAC domain of the protein and a copper-dependent component associated with the C-terminus of the protein and potentiated by involvement of the N-terminus. We hypothesise that copper binding call cause conversion of AS to a neurotoxic form via inter-protein interactions. (C) 2009 Elsevier Inc. All rights reserved