Structural characterisation of α-synuclein-membrane interactions and the resulting aggregation using small angle scattering
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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; Marlet, Frederik Ravnkilde; Moulin, Martine; Devos, Juliette M; Linse, Sara; Martel, Anne; Porcar, Lionel; Sparr, Emma; Pedersen, Martin Cramer; Roosen-Runge, Felix; Arleth, Lise; Buell, Alexander K.
In: Physical chemistry chemical physics : PCCP, Vol. 26, 2024, p. 10998-11013.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Structural characterisation of α-synuclein-membrane interactions and the resulting aggregation using small angle scattering
AU - Galvagnion, Céline
AU - Barclay, Abigail
AU - Makasewicz, Katarzyna
AU - Marlet, Frederik Ravnkilde
AU - Moulin, Martine
AU - Devos, Juliette M
AU - Linse, Sara
AU - Martel, Anne
AU - Porcar, Lionel
AU - Sparr, Emma
AU - Pedersen, Martin Cramer
AU - Roosen-Runge, Felix
AU - Arleth, Lise
AU - Buell, Alexander K
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1039/d3cp05928f
DO - 10.1039/d3cp05928f
M3 - Journal article
C2 - 38526443
VL - 26
SP - 10998
EP - 11013
JO - Physical Chemistry Chemical Physics
JF - Physical Chemistry Chemical Physics
SN - 1463-9076
ER -
ID: 387266820