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Fluorescence spectroscopy reveals N-terminal order in fibrillar forms of ?-synuclein.

ABSTRACT: The neuronal protein ?-synuclein (?S) plays a key role in Parkinson's disease, forming inclusions termed Lewy bodies and Lewy neurites. Recent improvements in cryo-electron diffraction and solid state NMR (ssNMR) have led to the elucidation of the structures of peptides derived from the ?S fibril core and full-length human ?S in fibrils. Despite the valuable insight offered by these methods, there are still several questions about the structures' relevance to pathological aggregates. Herein, we present fluorescence data collected in vitro under the conditions which fibrils are typically assembled. Our data suggest that, in solution, fibrils are largely structured as observed by ssNMR. However, we observe significant disparities in the ?S N-terminus as compared to ssNMR data, which provide insight on its important role in ?S aggregation and fibril structure.

SUBMITTER: Haney CM

PROVIDER: S-EPMC5961496 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Fluorescence spectroscopy reveals N-terminal order in fibrillar forms of α-synuclein.

Haney Conor M CM Petersson E James EJ

Chemical communications (Cambridge, England) 20180101 7

The neuronal protein α-synuclein (αS) plays a key role in Parkinson's disease, forming inclusions termed Lewy bodies and Lewy neurites. Recent improvements in cryo-electron diffraction and solid state NMR (ssNMR) have led to the elucidation of the structures of peptides derived from the αS fibril core and full-length human αS in fibrils. Despite the valuable insight offered by these methods, there are still several questions about the structures' relevance to pathological aggregates. Herein, we ...[more]

PMID: 29313531

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