Mapping long-range interactions in α-synuclein using spin-label NMR and ensemble molecular dynamics simulations
Mapping long-range interactions in α-synuclein using spin-label NMR and ensemble molecular dynamics simulations
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DOI：
10.1021/ja044834j
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发表时间：
2005-01-19
影响因子：
15
通讯作者：
Dobson, CM
中科院分区：
文献类型：
--
作者：
Dedmon, MM;Lindorff-Larsen, K;Dobson, CM
α-突触核蛋白在帕金森病(PD)的发病机制中起着关键作用。我们发现α-突触核蛋白的本征状态由广泛分布的构象组成，其系综平均流体动力学半径比随机卷曲结构的预期要小得多。这种部分缩合是由高电荷的C末端和蛋白质序列的一个大的疏水中心区域之间的相互作用驱动的。我们认为这种结构可以抑制α-突触核蛋白聚集体的形成，这被认为是导致帕金森病神经变性的细胞毒性物种。
The intrinsically disordered protein α-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). We show here that the native state of α-synuclein consists of a broad distribution of conformers with an ensemble-averaged hydrodynamic radius significantly smaller than that expected for a random coil structure. This partial condensation is driven by interactions between the highly charged C-terminus and a large hydrophobic central region of the protein sequence. We suggest that this structure could inhibit the formation of α-synuclein aggregates, which are thought to be the cytotoxic species responsible for neurodegeneration in PD.