Conserved core of amyloid fibrils of wild type and A30P mutant α-synuclein
Conserved core of amyloid fibrils of wild type and A30P mutant α-synuclein
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DOI：
10.1002/pro.570
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发表时间：
2011-02-01
期刊：
影响因子：
8
通讯作者：
Zweckstetter, Markus
中科院分区：
文献类型：
--
作者：
Cho, Min-Kyu;Kim, Hai-Young;Zweckstetter, Markus
神经包涵体的主要成分是帕金森氏病的病理标志是蛋白a-突触核蛋白（aS）的淀粉样原纤维。在这里，我们研究了疾病相关突变A30P是否不仅调节aS聚集动力学，而且改变淀粉样蛋白原纤维的结构。为此，我们优化了淬氢/氘交换与核磁共振光谱耦合的方法，并进行了二维质子探测高分辨率魔角旋转实验。综合数据表明，A30P突变不会引起aS淀粉样原纤维β -链的数量、位置和整体排列的改变。同时，纤维核内的几个残基保持纳秒动力学。我们得出结论，与家族性A30P突变相关的致病性增加不太可能是由突变诱导的aS聚集体构象改变引起的。
The major component of neural inclusions that are the pathological hallmark of Parkinson's disease are amyloid fibrils of the protein a-synuclein (aS). Here we investigated if the disease-related mutation A30P not only modulates the kinetics of aS aggregation, but also alters the structure of amyloid fibrils. To this end we optimized the method of quenched hydrogen/deuterium exchange coupled to NMR spectroscopy and performed two-dimensional proton-detected high-resolution magic angle spinning experiments. The combined data indicate that the A30P mutation does not cause changes in the number, location and overall arrangement of beta-strands in amyloid fibrils of aS. At the same time, several residues within the fibrillar core retain nano-second dynamics. We conclude that the increased pathogenicity related to the familial A30P mutation is unlikely to be caused by a mutation-induced change in the conformation of aS aggregates.