Winter Daniel L, Erce Melissa A, Wilkins Marc R
Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales , Sydney, New South Wales 2052, Australia.
J Proteome Res. 2014 Dec 5;13(12):5333-8. doi: 10.1021/pr500585p. Epub 2014 Nov 12.
Many proteins, including p53, the FoxO transcription factors, RNA polymerase II, pRb, and the chaperones, have extensive post-translational modifications (PTMs). Many of these modifications modulate protein-protein interactions, controlling interaction presence/absence and specificity. Here we propose the notion of the interaction code, a widespread means by which modifications are used to control interactions in the proteome. Minimal interaction codes are likely to exist on proteins that have two modifications and two or more interaction partners. By contrast, complex interaction codes are likely to be found on "date hub" proteins that have many interactions, many PTMs, or are targeted by many modifying and demodifying enzymes. Proteins with new interaction codes should be discoverable by examining protein interaction networks, annotated with PTMs and protein-modifying enzyme-substrate links. Multiple instances or combinations of phosphorylation, acetylation, methylation, O-GlcNAc, or ubiquitination will likely form interaction codes, especially when colocated on a protein's single interaction interface. A network-based example of code discovery is given, predicting the yeast protein Npl3p to have a methylation/phosphorylation-dependent interaction code.
许多蛋白质，包括p53、FoxO转录因子、RNA聚合酶II、视网膜母细胞瘤蛋白（pRb）以及分子伴侣，都有广泛的翻译后修饰（PTM）。其中许多修饰可调节蛋白质-蛋白质相互作用，控制相互作用的有无及特异性。在此，我们提出相互作用密码这一概念，这是一种广泛存在的方式，通过它修饰作用被用于控制蛋白质组中的相互作用。最小的相互作用密码可能存在于具有两种修饰和两个或更多相互作用伙伴的蛋白质上。相比之下，复杂的相互作用密码可能出现在具有许多相互作用、许多PTM或者被许多修饰和去修饰酶作用的“约会枢纽”蛋白上。通过检查用PTM以及蛋白质修饰酶-底物链接注释的蛋白质相互作用网络，应该能够发现具有新相互作用密码的蛋白质。磷酸化、乙酰化、甲基化、O-连接的N-乙酰葡糖胺化或泛素化的多个实例或组合可能会形成相互作用密码，尤其是当它们位于蛋白质的单个相互作用界面上时。文中给出了一个基于网络的密码发现示例，预测酵母蛋白Npl3p具有甲基化/磷酸化依赖性相互作用密码。
