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Ganglioside GM3 stimulates lipid-protein co-assembly in α-synuclein amyloid formation

Fridolf, Simon LU ; Pham, Quoc Dat LU ; Pallbo Arvidsson, Jon LU ; Bernfur, Katja LU ; Linse, Sara LU ; Topgaard, Daniel LU and Sparr, Emma LU (2023) In Biophysical Chemistry 293.
Abstract

Parkinson's disease is characterized by the aggregation of the presynaptic protein α-synuclein (αSyn), and its co-assembly with lipids and other cellular matter in the brain. Here we investigated lipid-protein co-assembly in a system composed of αSyn and model membranes containing the glycolipid ganglioside GM3. We quantified the uptake of lipids into the co-assembled aggregates and investigated how lipid molecular dynamics is altered by being present in the co-assemblies using solution 1H- and solid-state 13C NMR spectroscopy. Aggregate morphology was studied using cryo-TEM. The overall lipid uptake in the co-assembled aggregates was found to increase with the molar ratio of GM3 in the vesicles. The lipids present... (More)

Parkinson's disease is characterized by the aggregation of the presynaptic protein α-synuclein (αSyn), and its co-assembly with lipids and other cellular matter in the brain. Here we investigated lipid-protein co-assembly in a system composed of αSyn and model membranes containing the glycolipid ganglioside GM3. We quantified the uptake of lipids into the co-assembled aggregates and investigated how lipid molecular dynamics is altered by being present in the co-assemblies using solution 1H- and solid-state 13C NMR spectroscopy. Aggregate morphology was studied using cryo-TEM. The overall lipid uptake in the co-assembled aggregates was found to increase with the molar ratio of GM3 in the vesicles. The lipids present in the co-assembled aggregates have reduced acyl chain and headgroup dynamics compared to the protein-free bilayer system. These findings may improve our understanding of how different types of lipids can influence the composition of αSyn aggregates, which may have consequences for amyloid formation in vivo.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ganglioside, Lipid, NMR spectroscopy, Parkinson's disease, Protein aggregation, Vesicle, α-synuclein
in
Biophysical Chemistry
volume
293
article number
106934
publisher
Elsevier
external identifiers
  • pmid:36493587
  • scopus:85143882060
ISSN
0301-4622
DOI
10.1016/j.bpc.2022.106934
language
English
LU publication?
yes
id
0a490b15-b119-4060-b559-e83a5f80e3f5
date added to LUP
2023-12-07 14:54:01
date last changed
2024-04-20 10:12:28
@article{0a490b15-b119-4060-b559-e83a5f80e3f5,
  abstract     = {{<p>Parkinson's disease is characterized by the aggregation of the presynaptic protein α-synuclein (αSyn), and its co-assembly with lipids and other cellular matter in the brain. Here we investigated lipid-protein co-assembly in a system composed of αSyn and model membranes containing the glycolipid ganglioside GM3. We quantified the uptake of lipids into the co-assembled aggregates and investigated how lipid molecular dynamics is altered by being present in the co-assemblies using solution <sup>1</sup>H- and solid-state <sup>13</sup>C NMR spectroscopy. Aggregate morphology was studied using cryo-TEM. The overall lipid uptake in the co-assembled aggregates was found to increase with the molar ratio of GM3 in the vesicles. The lipids present in the co-assembled aggregates have reduced acyl chain and headgroup dynamics compared to the protein-free bilayer system. These findings may improve our understanding of how different types of lipids can influence the composition of αSyn aggregates, which may have consequences for amyloid formation <i>in vivo.</i></p>}},
  author       = {{Fridolf, Simon and Pham, Quoc Dat and Pallbo Arvidsson, Jon and Bernfur, Katja and Linse, Sara and Topgaard, Daniel and Sparr, Emma}},
  issn         = {{0301-4622}},
  keywords     = {{Ganglioside; Lipid; NMR spectroscopy; Parkinson's disease; Protein aggregation; Vesicle; α-synuclein}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Biophysical Chemistry}},
  title        = {{Ganglioside GM3 stimulates lipid-protein co-assembly in α-synuclein amyloid formation}},
  url          = {{http://dx.doi.org/10.1016/j.bpc.2022.106934}},
  doi          = {{10.1016/j.bpc.2022.106934}},
  volume       = {{293}},
  year         = {{2023}},
}