纤维
小泡
小角X射线散射
成核
生物物理学
化学
脂质双层
淀粉样蛋白(真菌学)
小角中子散射
蛋白质聚集
结晶学
膜
中子散射
散射
生物化学
生物
有机化学
光学
物理
无机化学
作者
Céline Galvagnion,Abigail Barclay,Katarzyna Makasewicz,Frederik Ravnkilde Marlet,Martine Moulin,Juliette M. Devos,Sara Linse,Anne Martel,Lionel Porcar,Emma Sparr,Martin Cramer Pedersen,Felix Roosen‐Runge,Lise Arleth,Alexander Kai Büll
标识
DOI:10.26434/chemrxiv-2023-6hsh2
摘要
The presence of amyloid fibrils is a hallmark of several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and amyloid β, can interact with lipids, and this interaction can strongly favor 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 vesicles formed from negatively charged lipids and their co-assembly into amyloid fibrils. We find that the lipid vesicles do not simply act as a surface that catalyses the nucleation reaction, but that lipid molecules take an active role in the reaction. The binding of α-synuclein to the lipid vesicles immediately induces a major structural change in the lipid assembly, which leads to a break-up into small, cylindrical and disc-like lipid-protein particles. This transition can be largely reversed by temperature changes or proteolytic protein removal. Incubation of these small, cylindrical and disc-like lipid-α-synuclein particles for several hours, however, yields amyloid fibril formation, whereby the lipids are incorporated into the fibrils.
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