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Structural characterisation of α-synuclein-membrane interactions and the resulting aggregation using small angle scattering

Galvagnion, Céline ; Barclay, Abigail ; Makasewicz, Katarzyna LU ; Marlet, Frederik Ravnkilde ; Moulin, Martine ; Devos, Juliette M. ; Linse, Sara LU ; Martel, Anne ; Porcar, Lionel and Sparr, Emma LU , et al. (2024) In Physical Chemistry Chemical Physics 26(14). p.10998-11013
Abstract

The presence of amyloid fibrils is a hallmark of several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and amyloid β, interact with lipids, and this interaction can strongly favour the formation of amyloid fibrils. In particular the primary nucleation step, i.e. the de novo formation of amyloid fibrils, has been shown to be accelerated by lipids. However, the exact mechanism of this acceleration is still mostly unclear. Here we use a range of scattering methods, such as dynamic light scattering (DLS) and small angle X-ray and neutron scattering (SAXS and SANS) to obtain structural information on the binding of α-synuclein to model membranes formed from negatively charged lipids and their co-assembly into... (More)

The presence of amyloid fibrils is a hallmark of several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and amyloid β, interact with lipids, and this interaction can strongly favour the formation of amyloid fibrils. In particular the primary nucleation step, i.e. the de novo formation of amyloid fibrils, has been shown to be accelerated by lipids. However, the exact mechanism of this acceleration is still mostly unclear. Here we use a range of scattering methods, such as dynamic light scattering (DLS) and small angle X-ray and neutron scattering (SAXS and SANS) to obtain structural information on the binding of α-synuclein to model membranes formed from negatively charged lipids and their co-assembly into amyloid fibrils. We find that the model membranes take an active role in the reaction. The binding of α synuclein to the model membranes immediately induces a major structural change in the lipid assembly, which leads to a break-up into small and mostly disc- or rod-like lipid-protein particles. This transition can be reversed by temperature changes or proteolytic protein removal. Incubation of the small lipid-α-synuclein particles for several hours, however, leads to amyloid fibril formation, whereby the lipids are incorporated into the amyloid fibrils.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physical Chemistry Chemical Physics
volume
26
issue
14
pages
16 pages
publisher
Royal Society of Chemistry
external identifiers
  • scopus:85189684400
  • pmid:38526443
ISSN
1463-9076
DOI
10.1039/d3cp05928f
language
English
LU publication?
yes
id
8d9ac7d2-188b-42bb-8cfb-dcaa319eb14f
date added to LUP
2024-04-26 14:26:37
date last changed
2024-06-21 19:29:03
@article{8d9ac7d2-188b-42bb-8cfb-dcaa319eb14f,
  abstract     = {{<p>The presence of amyloid fibrils is a hallmark of several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and amyloid β, interact with lipids, and this interaction can strongly favour the formation of amyloid fibrils. In particular the primary nucleation step, i.e. the de novo formation of amyloid fibrils, has been shown to be accelerated by lipids. However, the exact mechanism of this acceleration is still mostly unclear. Here we use a range of scattering methods, such as dynamic light scattering (DLS) and small angle X-ray and neutron scattering (SAXS and SANS) to obtain structural information on the binding of α-synuclein to model membranes formed from negatively charged lipids and their co-assembly into amyloid fibrils. We find that the model membranes take an active role in the reaction. The binding of α synuclein to the model membranes immediately induces a major structural change in the lipid assembly, which leads to a break-up into small and mostly disc- or rod-like lipid-protein particles. This transition can be reversed by temperature changes or proteolytic protein removal. Incubation of the small lipid-α-synuclein particles for several hours, however, leads to amyloid fibril formation, whereby the lipids are incorporated into the amyloid fibrils.</p>}},
  author       = {{Galvagnion, Céline and Barclay, Abigail and Makasewicz, Katarzyna and Marlet, Frederik Ravnkilde and Moulin, Martine and Devos, Juliette M. and Linse, Sara and Martel, Anne and Porcar, Lionel and Sparr, Emma and Pedersen, Martin Cramer and Roosen-Runge, Felix and Arleth, Lise and Buell, Alexander K.}},
  issn         = {{1463-9076}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{14}},
  pages        = {{10998--11013}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Physical Chemistry Chemical Physics}},
  title        = {{Structural characterisation of α-synuclein-membrane interactions and the resulting aggregation using small angle scattering}},
  url          = {{http://dx.doi.org/10.1039/d3cp05928f}},
  doi          = {{10.1039/d3cp05928f}},
  volume       = {{26}},
  year         = {{2024}},
}