High-density lipoprotein-like particle formation of Synuclein variants
High-density lipoprotein-like particle formation of Synuclein variants
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DOI：
10.1002/1873-3468.12543
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发表时间：
2017-01-01
期刊：
影响因子：
3.5
通讯作者：
Riek, Roland
中科院分区：
文献类型：
--
作者：
Eichmann, Cedric;Kumari, Pratibha;Riek, Roland
α-突触核蛋白(α-Syn)是一种溶液中固有的无序蛋白质，其纤维聚集是帕金森病(PD)的标志。虽然α-Syn的具体功能尚不清楚，但其高度的结构可塑性是α-Syn与生物膜相互作用的关键。最近，人们观察到α-Syn能够形成高密度脂蛋白样(HDL样)颗粒，这让人想起自组装的磷脂双层纳米盘。在这里，我们将我们生产α-Syn脂蛋白颗粒的制备方法扩展到β-和theta-Syn变体，以及与PD相关的家族性α-Syn突变。我们表明，所有人类SYN都可以形成稳定和均匀的具有不同形态的HDL样颗粒群体。我们的结果表征了单个Syn对这些颗粒形成能力的影响，并表明Syn HDL样颗粒既不会造成毒性，也不会导致PD中α-Syn的毒性相关损失。
alpha-Synuclein (alpha-Syn) is an intrinsically disordered protein in solution whose fibrillar aggregates are the hallmark of Parkinson's disease (PD). Although the specific function of alpha-Syn is still unclear, its high structural plasticity is key for the interactions of alpha-Syn with biological membranes. Recently, it has been observed that alpha-Syn is able to form high-density lipoprotein-like (HDL-like) particles that are reminiscent of self-assembling phospholipid bilayer nanodiscs. Here, we extended our preparation method for the production of alpha-Syn lipoprotein particles to the beta- and theta-Syn variants, and the PD-related familial alpha-Syn mutants. We show that all human Syns can form stable and homogeneous populations of HDL-like particles with distinct morphologies. Our results characterize the impact of the individual Syns on the formation capacity of these particles and indicate that Syn HDL-like particles are neither causing toxicity nor a toxicity-related loss of alpha-Syn in PD.