Toxic Amyloid Tape: A Novel Mixed Antiparallel/Parallel
β‑Sheet Structure Formed by Amyloid β‑Protein
on GM1 Clusters
Posted on 2018-10-11 - 14:03
The
abnormal aggregation of amyloid β-protein (Aβ)
is considered central in the pathogenesis of Alzheimer’s disease.
We focused on membrane-mediated amyloidogenesis and found that amyloid
fibrils formed on monosialoganglioside GM1 clusters were more toxic
than those formed in aqueous solution. In this study, we investigated
the structure of the toxic fibrils by Aβ-(1–40) in detail
in comparison with less-toxic fibrils formed in aqueous solution.
The less-toxic fibrils contain in-resister parallel β-sheets,
whereas the structure of the toxic fibrils is unknown. Atomic force
microscopy revealed that the toxic fibrils had a flat, tape-like morphology
composed of a single β-sheet layer. Isotope-edited infrared
spectroscopy indicated that almost the entire sequence of Aβ
is included in the β-sheet. Chemical cross-linking experiments
using Cys-substituted Aβs suggested that the fibrils mainly
contained both in-resister parallel and two-residue-shifted antiparallel
β-sheet structures. Solid-state NMR experiments also supported
this conclusion. Thus, the toxic fibrils were found to possess a novel
unique structure.
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Okada, Yuki; Okubo, Kaori; Ikeda, Keisuke; Yano, Yoshiaki; Hoshino, Masaru; Hayashi, Yoshio; et al. (2018). Toxic Amyloid Tape: A Novel Mixed Antiparallel/Parallel
β‑Sheet Structure Formed by Amyloid β‑Protein
on GM1 Clusters. ACS Publications. Collection. https://doi.org/10.1021/acschemneuro.8b00424
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AUTHORS (10)
YO
Yuki Okada
KO
Kaori Okubo
KI
Keisuke Ikeda
YY
Yoshiaki Yano
MH
Masaru Hoshino
YH
Yoshio Hayashi
YK
Yoshiaki Kiso
HI
Hikari Itoh-Watanabe
AN
Akira Naito
KM
Katsumi Matsuzaki
KEYWORDS
amyloid β- proteinβ- sheet layerβ- sheetsGM 1 Clusterstape-like morphologyβ- sheetSolid-state NMR experimentsToxic Amyloid Tapetwo-residue-shifted antiparallel β- sheet structuresmembrane-mediated amyloidogenesismonosialoganglioside GM 1 clustersAtomic force microscopychemical cross-linking experimentsamyloid fibrils