A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances
A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances
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DOI：
10.1016/j.cell.2015.09.053
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发表时间：
2015-10-22
期刊：
影响因子：
64.5
通讯作者：
Mann, Matthias
中科院分区：
文献类型：
--
作者：
Hein, Marco Y.;Hubner, Nina C.;Mann, Matthias
细胞的组织来自于蛋白质网络中的相互作用。相互作用组是严重依赖于相互作用的强度和连接蛋白质的细胞丰度，这两者跨越数量级。然而，这些方面尚未在全球范围内进行分析。在这里，我们已经生成了一个在近内源性控制下表达1，125个GFP标记蛋白的HeLa细胞系库，我们将其用作下一代相互作用调查的输入。使用定量蛋白质组学，我们检测特定的相互作用，估计相互作用的化学计量，并测量相互作用蛋白质的细胞丰度。这三个定量维度揭示了蛋白质网络由弱的亚化学计量相互作用主导，这些相互作用在定义网络拓扑结构中起着关键作用。少数稳定的复合物可以通过其独特的化学计量特征来识别。这项研究提供了一个连接数千种蛋白质的丰富的相互作用数据集，并介绍了一个定量网络分析的框架。
The organization of a cell emerges from the interactions in protein networks. The interactome is critically dependent on the strengths of interactions and the cellular abundances of the connected proteins, both of which span orders of magnitude. However, these aspects have not yet been analyzed globally. Here, we have generated a library of HeLa cell lines expressing 1,125 GFP-tagged proteins under near-endogenous control, which we used as input for a next-generation interaction survey. Using quantitative proteomics, we detect specific interactions, estimate interaction stoichiometries, and measure cellular abundances of interacting proteins. These three quantitative dimensions reveal that the protein network is dominated by weak, substoichiometric interactions that play a pivotal role in defining network topology. The minority of stable complexes can be identified by their unique stoichiometry signature. This study provides a rich interaction dataset connecting thousands of proteins and introduces a framework for quantitative network analysis.