Cholesterol-containing lipid nanodiscs promote an α-synuclein binding mode that accelerates oligomerization.
Algorithms
Benzothiazoles
/ chemistry
Cholesterol
/ chemistry
Humans
Kinetics
Lipid Bilayers
/ chemistry
Magnetic Resonance Spectroscopy
Maleates
/ chemistry
Membrane Lipids
/ chemistry
Microscopy, Atomic Force
Nanostructures
/ chemistry
Protein Binding
Protein Multimerization
Styrene
/ chemistry
Surface Plasmon Resonance
alpha-Synuclein
/ chemistry
amyloid oligomerization
cholesterol
fibrillation
lipid nanodiscs
solution-state NMR
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
revised:
28
07
2020
received:
03
11
2019
accepted:
01
09
2020
pubmed:
7
9
2020
medline:
28
7
2021
entrez:
6
9
2020
Statut:
ppublish
Résumé
Dysregulation of the biosynthesis of cholesterol and other lipids has been implicated in many neurological diseases, including Parkinson's disease. Misfolding of α-synuclein (α-Syn), the main actor in Parkinson's disease, is associated with changes in a lipid environment. However, the exact molecular mechanisms underlying cholesterol effect on α-Syn binding to lipids as well as α-Syn oligomerization and fibrillation remain elusive, as does the relative importance of cholesterol compared to other factors. We probed the interactions and fibrillation behaviour of α-Syn using styrene-maleic acid nanodiscs, containing zwitterionic and anionic lipid model systems with and without cholesterol. Surface plasmon resonance and thioflavin T fluorescence assays were employed to monitor α-Syn binding, as well as fibrillation in the absence and presence of membrane models.
Substances chimiques
Benzothiazoles
0
Lipid Bilayers
0
Maleates
0
Membrane Lipids
0
alpha-Synuclein
0
thioflavin T
2390-54-7
Styrene
44LJ2U959V
maleic acid
91XW058U2C
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1887-1905Informations de copyright
© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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