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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)14146-14154
Number of pages9
JournalJournal of Biological Chemistry
Volume293
Issue number36
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Gangliosides
Nanoclusters
Amyloid
Membranes
Alzheimer Disease
Neurodegenerative diseases
G(M1) Ganglioside
Lipids
Serum Amyloid A Protein
Sphingomyelins
Atomic Force Microscopy
Fourier Transform Infrared Spectroscopy
Neurodegenerative Diseases
Topography
Seed
Elongation
Atomic force microscopy
Seeds
Deposits
Monomers

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Amyloid- fibrils assembled on ganglioside-enriched membranes contain both parallel -sheets and turns. / Matsubara, Teruhiko; Yasumori, Hanaki; Ito, Koichiro; Shimoaka, Takafumi; Hasegawa, Takeshi; Sato, Toshinori.

In: Journal of Biological Chemistry, Vol. 293, No. 36, 01.01.2018, p. 14146-14154.

Research output: Contribution to journalArticle

Matsubara, Teruhiko ; Yasumori, Hanaki ; Ito, Koichiro ; Shimoaka, Takafumi ; Hasegawa, Takeshi ; Sato, Toshinori. / Amyloid- fibrils assembled on ganglioside-enriched membranes contain both parallel -sheets and turns. In: Journal of Biological Chemistry. 2018 ; Vol. 293, No. 36. pp. 14146-14154.
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