Unlike twins: an NMR comparison of two α-synuclein polymorphs featuring different toxicity.

Unlike twins: an NMR comparison of two α-synuclein polymorphs featuring different toxicity.
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与双胞胎不同:两种具有不同毒性的α-突触核蛋白多晶型物的NMR比较。

DOI:
10.1371/journal.pone.0090659
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Meier BH
Meier BH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gath J;Bousset L;Habenstein B;Melki R;Böckmann A;Meier BH

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我们使用固态 NMR 在结构上比较了 α-突触核蛋白的两种不同多晶型物,最近确定,这两种多晶型物显示出截然不同的生化特性、毒性和细胞向性。我们表明,这两种形式都可以作为纯多晶型物生产,但其二级结构有很大不同。虽然β-折叠是两种多晶型物的主要二级结构元素,但它们在元素数量及其分布方面明显不同。我们证明所有已识别的 β-折叠都具有两种多晶型物的注册内平行堆叠特征。这两种形式在晶胞中表现出不同的分子排列和独特的动态特征,同时共享高度灵活的 C 端结构域。使用可重复、明确的样品制备条件和记录相同的 NMR 实验可以直接比较结果。
We structurally compare, using solid-state NMR, two different polymorphs of α-synuclein which, as established recently, display contrasting biochemical properties, toxicity, and tropism for cells. We show that both forms, which can each be produced as a pure polymorph, are greatly different in secondary structure. While β-sheets are the dominating secondary structure elements for both polymorphs, they are markedly divergent in terms of number of elements, as well as their distribution. We demonstrate that all identified β-sheets feature an in-register parallel stacking for both polymorphs. The two forms show a different molecular arrangement in the unit cell and distinct dynamic features, while sharing a highly flexible C-terminal domain. The use of reproducible, well-identified conditions for sample preparation and the recording of identical NMR experiments allows for a direct comparison of the results.
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发表时间: 2010-02-09
期刊: BIOCHEMISTRY
影响因子: 2.9
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