Nanopore Analysis of β-Amyloid Peptide Aggregation Transition Induced by Small Molecules
Nanopore Analysis of β-Amyloid Peptide Aggregation Transition Induced by Small Molecules
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DOI：
10.1021/ac1029874
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发表时间：
2011-03-01
影响因子：
7.4
通讯作者：
Long, Yi-Tao
中科院分区：
文献类型：
--
作者：
Wang, Hai-Yan;Ying, Yi-Lun;Long, Yi-Tao
β-淀粉样蛋白42（A β 42）是淀粉样蛋白肽的主要形式，其存在于阿尔茨海默病（AD）患者的脑斑中，并且是淀粉样蛋白聚集体中最丰富的组分之一。A β 42聚集状态的信息对于理解淀粉样变性的病理过程是必不可少的。在这里，我们使用α-溶血素（α-HL）孔来探测A β 42在β-环糊精（β-CD）（A β 42聚集的促进剂）和刚果红（CR）（聚集的抑制剂）存在下的不同聚集转变。分析特征性的通过持续时间和阻断电流表明，β-CD和CR对A β 42的聚集具有相反的作用。单体A β 42肽的易位事件在振幅电流方面显著低于原丝，并且原丝以较长的持续时间被捕获在α-HL纳米孔中。CR通过减少聚集的原纤维形成而与A β 42及其肽原纤维结合。在该过程中，假定CR干扰聚集体中存在的分子间氢键。与CR相反，β-CD促进A β 42的聚集。这些差异可以通过使用生物学α-HL纳米孔监测相应的特征性阻断事件来容易地分析。
beta-Amyloid 42 (A beta 42) is the predominant form of the amyloid peptide, which is found in the plaques of the brains of Alzheimer's (AD) patients and is one of the most abundant components in amyloid aggregates. Information of the A beta 42 aggregation states is essential for developing an understanding of the pathologic process of amyloidoses. Here, we used alpha-hemolysin (alpha-HL) pores to probe the different aggregation transition of A beta 42 in the presence of beta-cyclodextrin (beta-CD), a promoter of A beta 42 aggregations, and in the presence of Congo red (CR), an inhibitor of aggregations. Analyzing the characteristic transit duration times and blockade currents showed that beta-CD and CR have opposite effects on the aggregation of A beta 42. Translocation events of the monomeric A beta 42 peptide were significantly lower in amplitude currents than protofilaments, and protofilaments were captured in the alpha-HL nanopore with a longer duration time. CR binds to A beta 42 and its peptide fibrils by reducing the aggregated fibrils formation. In this process it is assumed CR interferes with intermolecular hydrogen bonding present in the aggregates. In contrast to CR, beta-CD promotes the aggregation of A beta 42. These differences can readily be analyzed by monitoring the corresponding characteristic blockade events using a biological alpha-HL nanopore.