ANS Binding Reveals Common Features of Cytotoxic Amyloid Species
ANS Binding Reveals Common Features of Cytotoxic Amyloid Species
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DOI：
10.1021/cb1001203
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发表时间：
2010-08-01
影响因子：
4
通讯作者：
Yerbury, Justin J.
中科院分区：
文献类型：
--
作者：
Bolognesi, Benedetta;Kumita, Janet R.;Yerbury, Justin J.
由多种疾病相关的多肽和蛋白质形成的寡聚体与许多神经退行性疾病的毒性密切相关，如阿尔茨海默病。然而，毒物的确切性质仍有待确定。我们发现Aβ(1-42)的E22G(北极)变异体的前纤维聚集体与1-苯基-8-苯基-8-磺酸强烈结合，这种性质的变化与其细胞毒性的变化显著相关。此外，我们发现这种现象在其他淀粉样蛋白系统中也是常见的，例如野生型Aβ(1-42)、人类溶菌酶的159T变异体和SH3结构域。这些发现与一个模型一致，在该模型中，由于错误折叠的物种聚集而导致的疏水表面暴露是这些致病物种的关键和共同特征。
Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer's disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates of E22G (arctic) variant of the A beta(1-42) peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity. Moreover, we show that this phenomenon is common to other amyloid systems, such as wild-type A beta(1-42), the 159T variant of human lysozyme and an SH3 domain. These findings are consistent with a model in which the exposure of hydrophobic surfaces as a result of the aggregation of misfolded species is a crucial and common feature of these pathogenic species.