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

ABSTRACT: We structurally compare, using solid-state NMR, two different polymorphs of ?-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 ?-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 ?-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.

SUBMITTER: Gath J

PROVIDER: S-EPMC3944079 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Gath Julia J Bousset Luc L Habenstein Birgit B Melki Ronald R Böckmann Anja A Meier Beat H BH

PloS one 20140305 3

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 demons ...[more]

PMID: 24599158

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