Amyloid Fibrillation Kinetics: Insight from Atomistic Nucleation Theory
Amyloid Fibrillation Kinetics: Insight from Atomistic Nucleation Theory
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DOI：
10.1016/j.jmb.2011.05.032
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发表时间：
2011-08-05
影响因子：
5.6
通讯作者：
Auer, Stefan
中科院分区：
文献类型：
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作者：
Cabriolu, Raffaele;Auer, Stefan
当蛋白质片段(β-链)直接聚合成β-折叠时，我们在分子水平上考虑了由连续层状的β-折叠组成的纳米淀粉样纤维的成核过程。将原子成核理论(ANT)应用于β(2)-微球蛋白和淀粉样β(40)的淀粉样成核，使我们能够预测纤维核大小和纤维成核率作为蛋白质溶液过饱和度的函数。ANT的预测与最近的时间分辨光学实验进行了比较，在这些实验中，他们测量了蛋白质浓度和突变对蛋白质溶液中淀粉样纤维形成之前的初始滞后时间的影响。本文的分析揭示了纳米淀粉样纤维成核动力学的一般原理，并表明它可以在现有的新相成核的一般理论框架下处理。(C)2011爱思唯尔有限公司。保留所有权利。
We consider the nucleation of nanosized amyloid fibrils composed of successively layered beta-sheets at the molecular level when this process takes place by direct polymerization of protein segments (beta-strands) into beta-sheets. Application of the atomistic nucleation theory (ANT) to amyloid nucleation of beta(2)-microglobulin and amyloid beta(40) allows us to predict the fibril nucleus size and the fibril nucleation rate as functions of the supersaturation of the protein solution. The ANT predictions are compared to recent time-resolved optical experiments where they measure the effect of the protein concentration and mutations on the initial lag time before amyloid fibrils form in the protein solution. The presented analysis reveals the general principles underlying the nucleation kinetics of nanosized amyloid fibrils and indicates that it can be treated in the framework of existing general theories of the nucleation of new phases. (C) 2011 Elsevier Ltd. All rights reserved.