A Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication
A Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication
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DOI：
10.1016/j.cell.2017.12.006
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发表时间：
2018-01-11
期刊：
影响因子：
64.5
通讯作者：
Picotti, Paola
中科院分区：
文献类型：
--
作者：
Piazza, Ilaria;Kochanowski, Karl;Picotti, Paola
代谢物-蛋白质相互作用控制多种细胞过程，从而在维持细胞内稳态中发挥主要作用。代谢产物构成细胞中最大部分的分子，但我们对代谢产物-蛋白质相互作用组的了解落后于我们对蛋白质-蛋白质或蛋白质-DNA相互作用组的理解。在这里，我们提出了一个化学蛋白质组学的工作流程，直接在其原生环境中的代谢产物-蛋白质相互作用的系统识别。该方法确定了一个已知的和新的相互作用和结合位点在大肠杆菌的网络，我们证明了一些新发现的相互作用的功能相关性。我们的数据能够识别新的酶-底物关系和代谢物诱导的蛋白质复合物重塑的情况。我们的代谢产物-蛋白质相互作用组由1，678个相互作用和7，345个推定的结合位点组成。我们的数据揭示了化学通讯的功能和结构原则，阐明了酶混杂的流行和机制，并使提取的定量参数的代谢产物结合在蛋白质组范围内。
Metabolite-protein interactions control a variety of cellular processes, thereby playing a major role in maintaining cellular homeostasis. Metabolites comprise the largest fraction of molecules in cells, but our knowledge of the metabolite-protein interactome lags behind our understanding of protein-protein or protein-DNA interactomes. Here, we present a chemoproteomic workflow for the systematic identification of metabolite-protein interactions directly in their native environment. The approach identified a network of known and novel interactions and binding sites in Escherichia coli, and we demonstrated the functional relevance of a number of newly identified interactions. Our data enabled identification of new enzyme-substrate relationships and cases of metabolite-induced remodeling of protein complexes. Our metabolite-protein interactome consists of 1,678 interactions and 7,345 putative binding sites. Our data reveal functional and structural principles of chemical communication, shed light on the prevalence and mechanisms of enzyme promiscuity, and enable extraction of quantitative parameters of metabolite binding on a proteome-wide scale.