Quantifying interactions of β-synuclein and γ-synuclein with model membranes.
Quantifying interactions of β-synuclein and γ-synuclein with model membranes.
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DOI：
10.1016/j.jmb.2012.08.008
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发表时间：
2012-11-02
影响因子：
5.6
通讯作者：
Rhoades, Elizabeth
中科院分区：
文献类型：
--
作者：
Ducas, Vanessa C.;Rhoades, Elizabeth
关键词：
突触核蛋白是参与许多神经退行性病变[α-突触核蛋白和β-突触核蛋白（βS）]以及各种类型的癌症[γ-突触核蛋白（γS）]的蛋白质家族。虽然α-突触核蛋白和帕金森病之间的联系已经建立，但最近的证据将βS的点突变与路易体痴呆联系起来。γS的过表达与肿瘤的转移和耐药性有关。尽管它们在如此多种疾病中普遍存在，但突触核蛋白的天然功能仍不清楚。它们在其N-末端区域具有脂质结合基序，这表明在体内与生物膜相互作用。在这项研究中，我们使用荧光相关光谱来监测βS和γS与模型膜的结合性质，并确定相互作用的自由能。我们的研究结果表明，最强烈的相互作用的存在下，阴离子脂质和双层曲率，而膜流动性起着非常小的作用。定量βS和γS的脂质结合特性为控制蛋白质-膜相互作用的潜在因素提供了额外的见解。这些见解不仅与这些蛋白质的天然功能相关，而且还强调了它们对由这些相互作用的干扰介导或特征的病理状况的贡献。
The synucleins are a family of proteins involved in numerous neurodegenerative pathologies [α-synuclein and β-synuclein (βS)], as well as in various types of cancers [γ-synuclein (γS)]. While the connection between α-synuclein and Parkinson's disease is well established, recent evidence links point mutants of βS to dementia with Lewy bodies. Overexpression of γS has been associated with enhanced metastasis and cancer drug resistance. Despite their prevalence in such a variety of diseases, the native functions of the synucleins remain unclear. They have a lipid-binding motif in their N-terminal region, which suggests interactions with biological membranes in vivo. In this study, we used fluorescence correlation spectroscopy to monitor the binding properties of βS and γS to model membranes and to determine the free energy of the interactions. Our results show that the interactions are most strongly affected by the presence of both anionic lipids and bilayer curvature, while membrane fluidity plays a very minor role. Quantifying the lipid-binding properties of βS and γS provides additional insights into the underlying factors governing the protein–membrane interactions. Such insights not only are relevant to the native functions of these proteins but also highlight their contributions to pathological conditions that are either mediated or characterized by perturbations of these interactions.
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DOI：
10.1083/jcb.200207113
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ehehalt R;Keller P;Haass C;Thiele C;Simons K
通讯作者：
Simons K
影响因子：
2.9
作者：
CHEETHAM, JJ;WACHTEL, E;EPAND, RM
通讯作者：
EPAND, RM
影响因子：
12.4
作者：
Gorbatyuk, Oleg S.;Li, Shoudong;Muzyczka, Nicholas
通讯作者：
Muzyczka, Nicholas
DOI：
10.1016/b978-044453219-0.50003-9
发表时间：
2008-01-01
期刊：
BIOCHEMISTRY OF LIPIDS, LIPOPROTEINS AND MEMBRANES, 5TH EDITION
影响因子：
--
作者：
Dowhan, William;Bogdanov, Mikhail;Mileykovskaya, Eugenia
通讯作者：
Mileykovskaya, Eugenia
DOI：
10.1073/pnas.1005005107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Greten-Harrison, Becket;Polydoro, Manuela;Chandra, Sreeganga S.
通讯作者：
Chandra, Sreeganga S.