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

The Journal of Biological Chemistry
Teruhiko MatsubaraToshinori Sato

Abstract

Some protein and peptide aggregates, such as those of amyloid-β protein (Aβ), are neurotoxic and have been implicated in several neurodegenerative diseases. Aβ 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 Aβ deposits at such nanoclusters is known, the mechanism of their assembly and the relationship between Aβ secondary structure and topography are still unclear. Here, we first confirmed by atomic force microscopy that Aβ40 fibrils can be obtained by incubating seed-free Aβ40 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 β-sheets, whereas self-assembled Aβ40 molecules formed antiparallel β-sheets. We also found that the fibrils obtained at GM1-rich nanoclusters were generated from turn Aβ40 Our findings indicate that Aβ generally self-assembles into antiparallel β-structures but can also form protofibrils with parallel β-sheets by interacting with gan...Continue Reading

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Citations

Jun 14, 2019·Chemical Society Reviews·Michael C OwenBirgit Strodel
Jul 6, 2019·Protein Science : a Publication of the Protein Society·Atul K SrivastavaStephen C Meredith
Sep 13, 2020·Membranes·Vladimir Rudajev, Jiri Novotny
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Jan 26, 2021·ACS Chemical Neuroscience·Siddhartha BanerjeeYuri L Lyubchenko
Feb 3, 2021·Biophysical Chemistry·Fulvio Grigolato, Paolo Arosio
Oct 30, 2020·Frontiers in Neuroscience·Simonetta SipioneVaibhavi Kadam
Apr 4, 2021·International Journal of Biological Macromolecules·Willy SmeraldaAurélie Malzert-Fréon
May 25, 2021·Biochemistry·Jay M PittmanStephen C Meredith
Mar 7, 2020·Biochimica Et Biophysica Acta. Biomembranes·Katsumi Matsuzaki

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