Common structural features of toxic intermediates from α-synuclein and GroES fibrillogenesis detected using cryogenic coherent X-ray diffraction imaging

Hiroshi Kameda, Sayaka Usugi, Mana Kobayashi, Naoya Fukui, Seki Lee, Kunihiro Hongo, Tomohiro Mizobata, Yuki Sekiguchi, Yu Masaki, Amane Kobayashi, Tomotaka Oroguchi, Masayoshi Nakasako, Yuki Takayama, Masaki Yamamoto, Yasushi Kawata

研究成果: Article査読

4 被引用数 (Scopus)

抄録

The aggregation and deposition of α-synuclein (αSyn) in neuronal cells is correlated to pathogenesis of Parkinson's disease. Although the mechanism of αSyn aggregation and fibril formation has been studied extensively, the structural hallmarks that are directly responsible for toxicity toward cells are still under debate. Here, we have compared the structural characteristics of the toxic intermediate molecular species of αSyn and similar toxic species of another protein, GroES, using coherent X-ray diffraction analysis. Using coherent X-ray free electron laser pulses of SACLA, we analysed aSyn and GroES fibril intermediate species and characterized various aggregate structures. Unlike previous studies where an annular oligomeric form of αSyn was identified, particle reconstruction from scattering traces suggested that the specific forms of the toxic particles were varied, with the sizes of the particles falling within a specific range. We did however discover a common structural feature in both αSyn and GroES samples; the edges of the detected particles were nearly parallel and produced a characteristic diffraction pattern in the diffraction experiments. The presence of parallel-edged particles in toxic intermediates of αSyn and GroES fibrillogenesis pointed towards a plausible common molecular interface that leads to the formation of mature fibrils.

本文言語English
ページ(範囲)55-65
ページ数11
ジャーナルJournal of biochemistry
161
1
DOI
出版ステータスPublished - 2017 1 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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