Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation in Alzheimer's Disease
Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation in Alzheimer's Disease
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DOI：
10.1002/cphc.201600706
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发表时间：
2016-11-01
期刊：
影响因子：
2.9
通讯作者：
Lapidus, Lisa J.
中科院分区：
文献类型：
--
作者：
Acharya, Srabasti;Srivastava, Kinshuk R.;Lapidus, Lisa J.
测量单体阿尔茨海默（A β）肽的重构或分子内扩散的速率，并且在更可能聚集的条件下，肽扩散显著减慢，这允许双分子缔合被启动。通过使用Trp-Cys接触淬灭的方法，观察到A β 40（其缓慢聚集）的重构速率比A β（42）（其快速聚集）的重构速率快约5倍。此外，A β（42）的重构速率在更高的pH下加速，这减缓了聚集，并且在聚集抑制剂姜黄素的存在下。测量的重构速率能够预测Ab肽的早期聚集行为，并为为什么A β（42）比A β（40）更容易聚集提供动力学基础，尽管只有两个氨基酸的差异。
The rate of reconfiguration-or intramolecular diffusion-of monomeric Alzheimer (A beta) peptides is measured and, under conditions that aggregation is more likely, peptide diffusion slows down significantly, which allows bimolecular associations to be initiated. By using the method of Trp-Cys contact quenching, the rate of reconfiguration is observed to be about five times faster for A beta 40, which aggregates slowly, than that for A beta(42), which aggregates quickly. Furthermore, the rate of reconfiguration for A beta(42) speeds up at higher pH, which slows aggregation, and in the presence of the aggregation inhibitor curcumin. The measured reconfiguration rates are able to predict the early aggregation behavior of the Ab peptide and provide a kinetic basis for why A beta(42) is more prone to aggregation than A beta(40), despite a difference of only two amino acids.