α-Synuclein-induced tubule formation in lipid bilayers.
α-Synuclein-induced tubule formation in lipid bilayers.
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DOI：
10.1021/jp1121917
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发表时间：
2011-05-19
影响因子：
3.3
通讯作者：
Hovis, Jennifer S.
中科院分区：
文献类型：
--
作者：
Pandey, Anjan P.;Haque, Farzin;Rochet, Jean-Christophe;Hovis, Jennifer S.
α-突触核蛋白是一种突触前蛋白，与磷脂膜结合，参与帕金森病 (PD) 的发病机制。在本文中，我们描述了在含有 15-35 mol% 阴离子脂质的膜中添加野生型 α-突触核蛋白 (WT) 和三种家族性 PD 突变体（A53T、A30P 和 E46K）的效果。观察到膜中小管的形成程度取决于 α-突触核蛋白变体、阴离子脂质含量和蛋白质浓度。对于所有四种变体，小管形成随着阴离子脂质含量的增加而减少。 A30P 和 E46K 比 WT 或 A53T 更容易观察到小管。结果与模型一致，其中α-突触核蛋白的螺旋含量随着阴离子脂质含量的增加而增加，并且具有低螺旋含量的α-突触核蛋白构象异构体具有诱导小管形成的高倾向。这项工作与我们实验室之前的工作相结合（Pandey 等人，Biophys. J. 2009）表明，对于 WT 吸附，当阴离子脂质浓度小于 30 mol%（小管形成）或大于 40 mol%（双层重组、蛋白质聚集）时，蛋白质的吸附会对膜产生有害影响。
α-Synuclein is a presynaptic protein that binds to phospholipid membranes and is involved in the pathogenesis of Parkinson's disease (PD). In this paper we describe the effects of adding wild-type α-synuclein (WT) and three familial PD mutants (A53T, A30P and E46K) to membranes containing 15–35 mol % anionic lipid. Tubules were observed to form in the membranes to an extent that depended on the α-synuclein variant, the anionic lipid content and the protein concentration. For all four variants tubule formation decreased with increasing anionic lipid content. Tubules were more readily observed with A30P and E46K than with WT or A53T. The results are consistent with a model wherein the helical content of α-synuclein increases with increasing anionic lipid content, and α-synuclein conformers with low helical content have a high propensity to induce tubule formation. This work, combined with previous work from our laboratory (Pandey et al., Biophys. J. 2009), shows that for WT adsorption of the protein has deleterious effects on the membrane when the anionic lipid concentration is less than 30 mol % (tubule formation) or greater than 40 mol % (re-organization of the bilayer, clustering of protein).
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DOI：
10.1111/j.1600-0854.2008.00853.x
发表时间：
2009-02
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Ben Gedalya T;Loeb V;Israeli E;Altschuler Y;Selkoe DJ;Sharon R
通讯作者：
Sharon R
影响因子：
2.9
作者：
Bodner, Christina R.;Maltsev, Alexander S.;Dobson, Christopher M.;Bax, Ad
通讯作者：
Bax, Ad
影响因子：
3.3
作者：
Haque, Farzin;Pandey, Anjan P.;Cambrea, Lee R.;Rochet, Jean-Christophe;Hovis, Jennifer S.
通讯作者：
Hovis, Jennifer S.
影响因子：
64.8
作者：
Ford, MGJ;Mills, IG;McMahon, HT
通讯作者：
McMahon, HT
影响因子：
8
作者：
Bussell, R;Ramlall, TF;Eliezer, D
通讯作者：
Eliezer, D