Adsorption of alpha-synuclein on lipid bilayers: modulating the structure and stability of protein assemblies.
Adsorption of alpha-synuclein on lipid bilayers: modulating the structure and stability of protein assemblies.
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DOI：
10.1021/jp1006704
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发表时间：
2010-03-25
影响因子：
3.3
通讯作者：
Hovis, Jennifer S.
中科院分区：
文献类型：
--
作者：
Haque, Farzin;Pandey, Anjan P.;Cambrea, Lee R.;Rochet, Jean-Christophe;Hovis, Jennifer S.
α-突触核蛋白与磷脂膜的相互作用已经用支持的脂质双层和落射荧光显微镜检查。该膜含有磷脂酰胆碱（PC）和磷脂酸（PA），在生理pH值下混合。蛋白质吸附后，脂质进行液-液相分离成PC丰富和PA丰富的地区。蛋白质优先吸附到PA富集区域。α-突触核蛋白的吸附和随后的聚集通过调节几个参数来探测：脂质上的电荷、蛋白质上的电荷和筛选环境。促进最大程度的吸附的条件导致结构上异质的聚集体，而相对均匀的聚集体观察到的条件下，吸附不容易发生。我们观察到系统的不同改变导致不同程度的聚集和不同的聚集结构，这对药物发现提出了挑战。也就是说，旨在中和α-突触核蛋白的疗法必须靶向广泛的潜在毒性的膜结合组装体。
The interaction of α-synuclein with phospholipid membranes has been examined using supported lipid bilayers and epi-fluorescence microscopy. The membranes contained phosphatidylcholine (PC) and phosphatidic acid (PA), which mix at physiological pH. Upon protein adsorption the lipids undergo fluid-fluid phase separation into PC-rich and PA-rich regions. The protein preferentially adsorbs to the PA-rich regions. The adsorption and subsequent aggregation of α-synuclein was probed by tuning several parameters: the charge on the lipids, the charge on the protein, and the screening environment. Conditions which promoted the greatest extent of adsorption resulted in structurally heterogeneous aggregates, while comparatively homogeneous aggregates were observed under conditions whereby adsorption did not occur as readily. Our observation that different alterations to the system lead to different degrees of aggregation and different aggregate structures poses a challenge for drug discovery. Namely, therapies aimed at neutralizing α-synuclein must target a broad range of potentially toxic, membrane-bound assemblies.
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影响因子：
2.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
56.9
作者：
Conway, KA;Rochet, JC;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
2.4
作者：
Kucerka, N;Tristram-Nagle, S;Nagle, JF
通讯作者：
Nagle, JF
DOI：
10.1073/pnas.97.2.571
发表时间：
2000-01-18
影响因子：
11.1
作者：
Conway, KA;Lee, SJ;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
2
作者：
Garidel, P;Johann, C;Blume, A
通讯作者：
Blume, A