Absolute correlation between lag time and growth rate in the spontaneous formation of several amyloid-like aggregates and fibrils
Absolute correlation between lag time and growth rate in the spontaneous formation of several amyloid-like aggregates and fibrils
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DOI：
10.1016/j.jmb.2006.11.009
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发表时间：
2007-02-02
影响因子：
5.6
通讯作者：
Faendrich, Marcus
中科院分区：
文献类型：
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作者：
Faendrich, Marcus
多肽聚集体（包括淀粉样原纤维和朊病毒）的形成是一个生物化学过程，在其与衰老和神经退行性变相关的背景下引起了相当大的兴趣。聚集通常发生在滞后期和生长期，其反映了潜在的成核-聚合机制。虽然成核倾向可以从滞后时间t（l）估计，但是生长效率由生长速率k（g）表示。在这里，我分析了来自总共298个样品的绝对k（g）和t（l）值，这些样品是从胰岛素、胰高血糖素和阿尔茨海默氏病A β（1-40）肽的不同序列变体制备的。尽管这些样本的聚集条件不同，但系统比较揭示了k（g）与t（l）曲线的总体相似性。该图很容易与简单方程k（g）= alpha/t（l）拟合，并使用4.5的比例因子alpha。与k（g）和t（l）的个体值基本上取决于序列和环境参数相比，α似乎受这些因素的影响要小得多。这些数据表明，不同的淀粉样蛋白样纤维和聚集体的成核行为的机械相似性。(c)2006爱思唯尔有限公司保留所有权利。
The formation of polypeptide aggregates, including amyloid fibrils and prions, is a biochemical process of considerable interest in the context of its association with ageing and neurodegeneration. Aggregation occurs typically with a lag phase and a growth phase that reflect an underlying nucleation-polymerisation mechanism. While the propensity of nucleation can be estimated from the lag time t(l), the efficiency of growth is represented by the growth rate k(g). Here, I have analysed the absolute k(g) and t(l) values from a total of 298 samples prepared from insulin, glucagon and different sequence variants of the Alzheimer's A beta(1-40) peptide. Although these samples differ in the conditions of aggregation, systematic comparison reveals an overall similarity in the plot of k(g) versus t(l). The plot fits readily with the simple equation k(g) = alpha/t(l) and by using a proportionality factor alpha of 4.5. In contrast to the individual values of k(g) and t(l) that depend substantially on sequential and environmental parameters, alpha seems much less affected by such factors. These data suggest mechanistic similarities in the nucleation behaviour of different amyloid-like fibrils and aggregates. (c) 2006 Elsevier Ltd. All rights reserved.