Prediction of aggregation-prone regions in structured proteins
Prediction of aggregation-prone regions in structured proteins
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DOI：
10.1016/j.jmb.2008.05.013
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发表时间：
2008-07-04
影响因子：
5.6
通讯作者：
Vendruscolo, Michele
中科院分区：
文献类型：
--
作者：
Tartaglia, Gian Gaetano;Pawar, Amol P.;Vendruscolo, Michele
我们提出了一种方法来预测区域的序列的肽和蛋白质，是最重要的，在促进其聚集和淀粉样蛋白的形成。该方法扩展了以前的方法，允许这样的预测进行的条件下，有关分子可以折叠或包含一个显着程度的持久性结构。为了实现该结果，该方法仅使用氨基酸序列的知识来同时估计折叠和聚集的倾向以及这两种类型的倾向竞争的方式。我们说明了它的应用程序的一组肽和蛋白质都与疾病相关和不相关的方法。我们的研究结果表明，不仅具有高的内在聚集倾向的蛋白质的区域可以被确定在一个强大的方式，但也在单体形式的这些区域的结构背景是至关重要的，以确定其在聚集过程中的实际作用。(C)2008爱思唯尔有限公司保留所有权利。
We present a method for predicting the regions of the sequences of peptides and proteins that are most important in promoting their aggregation and amyloid formation. The method extends previous approaches by allowing such predictions to be carried out for conditions under which the molecules concerned can be folded or contain a significant degree of persistent structure. In order to achieve this result, the method uses only knowledge of the sequence of amino acids to estimate simultaneously both the propensity for folding and aggregation and the way in which these two types of propensity compete. We illustrate the approach by its application to a set of peptides and proteins both associated and not associated with disease. Our results show not only that the regions of a protein with a high intrinsic aggregation propensity can be identified in a robust manner but also that the structural context of such regions in the monomeric form is crucial for determining their actual role in the aggregation process. (C) 2008 Elsevier Ltd. All rights reserved.