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通过整合结构推断蛋白质-蛋白质相互作用网络中的时间维度:以p53为例

Towards inferring time dimensionality in protein-protein interaction networks by integrating structures: the p53 example.

作者信息

Tuncbag Nurcan, Kar Gozde, Gursoy Attila, Keskin Ozlem, Nussinov Ruth

机构信息

Koc University, Center for Computational Biology and Bioinformatics, College of Engineering, Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey.

出版信息

Mol Biosyst. 2009 Dec;5(12):1770-8. doi: 10.1039/B905661K.

Abstract

Inspection of protein-protein interaction maps illustrates that a hub protein can interact with a very large number of proteins, reaching tens and even hundreds. Since a single protein cannot interact with such a large number of partners at the same time, this presents a challenge: can we figure out which interactions can occur simultaneously and which are mutually excluded? Addressing this question adds a fourth dimension into interaction maps: that of time. Including the time dimension in structural networks is an immense asset; time dimensionality transforms network node-and-edge maps into cellular processes, assisting in the comprehension of cellular pathways and their regulation. While the time dimensionality can be further enhanced by linking protein complexes to time series of mRNA expression data, current robust, network experimental data are lacking. Here we outline how, using structural data, efficient structural comparison algorithms and appropriate datasets and filters can assist in getting an insight into time dimensionality in interaction networks; in predicting which interactions can and cannot co-exist; and in obtaining concrete predictions consistent with experiment. As an example, we present p53-linked processes.

摘要

对蛋白质-蛋白质相互作用图谱的检查表明,一个中心蛋白可以与大量蛋白质相互作用,数量可达数十甚至数百个。由于单个蛋白质无法同时与如此大量的伙伴相互作用,这就带来了一个挑战:我们能否弄清楚哪些相互作用可以同时发生,哪些是相互排斥的?解决这个问题为相互作用图谱增添了第四个维度:时间维度。将时间维度纳入结构网络是一项巨大的财富;时间维度将网络节点和边的图谱转化为细胞过程,有助于理解细胞途径及其调控。虽然通过将蛋白质复合物与mRNA表达数据的时间序列相联系可以进一步增强时间维度,但目前缺乏可靠的网络实验数据。在这里,我们概述了如何利用结构数据、高效的结构比较算法以及合适的数据集和筛选器,来帮助深入了解相互作用网络中的时间维度;预测哪些相互作用可以共存,哪些不能共存;以及获得与实验一致的具体预测。作为一个例子,我们展示了与p53相关的过程。

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