Binding affinity of amyloid oligomers to cellular membranes is a generic indicator of cellular dysfunction in protein misfolding diseases.
Binding affinity of amyloid oligomers to cellular membranes is a generic indicator of cellular dysfunction in protein misfolding diseases.
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DOI：
10.1038/srep32721
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发表时间：
2016-09-13
影响因子：
4.6
通讯作者：
Cecchi C
中科院分区：
文献类型：
--
作者：
Evangelisti E;Cascella R;Becatti M;Marrazza G;Dobson CM;Chiti F;Stefani M;Cecchi C
肽或蛋白质从其可溶性天然状态转化为难治性淀粉样蛋白沉积物与多种人类疾病相关。在聚集过程中形成的错误折叠的蛋白质寡聚体已被鉴定为许多此类病症中的主要病原体。在这里，我们显示了从模型蛋白质HypF-N形成的不同类型的寡聚体与神经元细胞的结合程度和质膜的GM 1含量之间的定量关系。此外，在与阿尔茨海默病相关的Aβ42肽寡聚体中观察到非常相似的行为。进一步的分析揭示了在触发细胞损伤的跨神经元膜的Ca 2+内流水平与结合至膜的寡聚物种类的分数之间存在线性相关性。我们的研究结果表明，神经元细胞对不同类型的错误折叠的低聚物组件的易感性直接关系到这种低聚物与细胞膜的结合程度。
The conversion of peptides or proteins from their soluble native states into intractable amyloid deposits is associated with a wide range of human disorders. Misfolded protein oligomers formed during the process of aggregation have been identified as the primary pathogenic agents in many such conditions. Here, we show the existence of a quantitative relationship between the degree of binding to neuronal cells of different types of oligomers formed from a model protein, HypF-N, and the GM1 content of the plasma membranes. In addition, remarkably similar behavior is observed for oligomers of the Aβ42 peptide associated with Alzheimer’s disease. Further analysis has revealed the existence of a linear correlation between the level of the influx of Ca2+ across neuronal membranes that triggers cellular damage, and the fraction of oligomeric species bound to the membrane. Our findings indicate that the susceptibility of neuronal cells to different types of misfolded oligomeric assemblies is directly related to the extent of binding of such oligomers to the cellular membrane.
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影响因子：
4.8
作者：
Ladiwala, Ali Reza A.;Litt, Jeffrey;Tessier, Peter M.
通讯作者：
Tessier, Peter M.
影响因子：
3.9
作者：
Cizas, Paulius;Budvytyte, Rima;Morkuniene, Ramune;Moldovan, Radu;Broccio, Matteo;Loesche, Mathias;Niaura, Gediminas;Valincius, Gintaras;Borutaite, Vilmante
通讯作者：
Borutaite, Vilmante
DOI：
10.1073/pnas.1218402110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Cohen, Samuel I. A.;Linse, Sara;Knowles, Tuomas P. J.
通讯作者：
Knowles, Tuomas P. J.
影响因子：
4.8
作者：
De Felice, Fernanda G.;Velasco, Pauline T.;Klein, William L.
通讯作者：
Klein, William L.
影响因子：
4.8
作者：
Kostylev, Mikhail A.;Kaufman, Adam C.;Strittmatter, Stephen M.
通讯作者：
Strittmatter, Stephen M.