Amyloid- fibrils assembled on ganglioside-enriched membranes contain both parallel -sheets and turns

Teruhiko Matsubara, Hanaki Yasumori, Koichiro Ito, Takafumi Shimoaka, Takeshi Hasegawa, Toshinori Sato

研究成果: Article査読

20 被引用数 (Scopus)

抄録

Some protein and peptide aggregates, such as those of amyloid- protein (A), are neurotoxic and have been implicated in several neurodegenerative diseases. A accumulates at nanoclusters enriched in neuronal lipids called gangliosides in the presynaptic neuronal membrane, and the resulting oligomeric and/or fibrous forms accelerate the development of Alzheimer’s disease. Although the presence of A deposits at such nanoclusters is known, the mechanism of their assembly and the relationship between A secondary structure and topography are still unclear. Here, we first confirmed by atomic force microscopy that A40 fibrils can be obtained by incubating seed-free A40 monomers with a membrane composed of sphingomyelin, cholesterol, and the ganglioside GM1. Using Fourier transform infrared (FTIR) reflection–absorption spectroscopy, we then found that these lipid-associated fibrils contained parallel -sheets, whereas self-assembled A40 molecules formed antiparallel -sheets. We also found that the fibrils obtained at GM1-rich nanoclusters were generated from turn A40. Our findings indicate that A generally self-assembles into antiparallel -structures but can also form protofibrils with parallel -sheets by interacting with ganglioside-bound A. We concluded that by promoting the formation of parallel -sheets, highly ganglioside-enriched nanoclusters help accelerate the elongation of A fibrils. These results advance our understanding of ganglioside-induced A fibril formation in neuronal membranes and may help inform the development of additional therapies for Alzheimer’s disease.

本文言語English
ページ(範囲)14146-14154
ページ数9
ジャーナルJournal of Biological Chemistry
293
36
DOI
出版ステータスPublished - 2018 9 7

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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