The fold of α-synuclein fibrils
The fold of α-synuclein fibrils
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DOI：
10.1073/pnas.0712179105
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发表时间：
2008-06-24
影响因子：
11.1
通讯作者：
Riek, Roland
中科院分区：
文献类型：
--
作者：
Vilar, Marcal;Chou, Hui-Ting;Riek, Roland
蛋白质聚集成淀粉样原纤维与几种神经退行性疾病有关。在帕金森病中，a-突触核蛋白（α -syn）通过中间体从单体聚集成淀粉样原纤维被认为是毒性疾病的致病机制。在这里，我们通过各种生物物理方法研究了淀粉样蛋白状态下a-syn的结构。淬火氢/氘交换核磁共振光谱鉴定出纤维核心内含有35-96残基的5条β -链，淀粉样原纤维包含纤维核心残基30-110的固态核磁共振数据证实了β -片二级结构的存在。数据表明β 1-链与β 2、β 2与β 3、β 3与β 4、β 4与β 5相互作用。高分辨率低温电子显微镜显示原丝边界约为2 x 3.5 nm。结合这些数据和已发表的结构研究，提出并讨论了原纤维中的α -syn折叠。
The aggregation of proteins into amyloid fibrils is associated with several neurodegenerative diseases. In Parkinson's disease it is believed that the aggregation of a-synuclein (alpha-syn) from monomers by intermediates into amyloid fibrils is the toxic disease-causative mechanism. Here, we studied the structure of a-syn in its amyloid state by using various biophysical approaches. Quenched hydrogen/deuterium exchange NMR spectroscopy identified five beta-strands within the fibril core comprising residues 35-96 and solid-state NMR data from amyloid fibrils comprising the fibril core residues 30-110 confirmed the presence of beta-sheet secondary structure. The data suggest that beta 1-strand interacts with beta 2, beta 2 with beta 3, beta 3 with beta 4, and beta 4 with beta 5. High-resolution cryoelectron microscopy revealed the protofilament boundaries of approximate to 2 x 3.5 nm. Based on the combination of these data and published structural studies, a fold of alpha-syn in the fibrils is proposed and discussed.