Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, London, United Kingdom.
Elife. 2021 May 21;10:e65358. doi: 10.7554/eLife.65358.
Multisite modification is a basic way of conferring functionality to proteins and a key component of post-translational modification networks. Additional interest in multisite modification stems from its capability of acting as complex information processors. In this paper, we connect two seemingly disparate themes: symmetry and multisite modification. We examine different classes of random modification networks of substrates involving separate or common enzymes. We demonstrate that under different instances of symmetry of the modification network (invoked explicitly or implicitly and discussed in the literature), the biochemistry of multisite modification can lead to the symmetry being broken. This is shown computationally and consolidated analytically, revealing parameter regions where this can (and in fact does) happen, and characteristics of the symmetry-broken state. We discuss the relevance of these results in situations where exact symmetry is not present. Overall, through our study we show how symmetry breaking (i) can confer new capabilities to protein networks, including concentration robustness of different combinations of species (in conjunction with multiple steady states); (ii) could have been the basis for ordering of multisite modification, which is widely observed in cells; (iii) can significantly impact information processing in multisite modification and in cell signalling networks/pathways where multisite modification is present; and (iv) can be a fruitful new angle for engineering in synthetic biology and chemistry. All in all, the emerging conceptual synthesis provides a new vantage point for the elucidation and the engineering of molecular systems at the junction of chemical and biological systems.
多位点修饰是赋予蛋白质功能的一种基本方式，也是翻译后修饰网络的关键组成部分。对多位点修饰的额外关注源于其作为复杂信息处理器的能力。在本文中，我们将两个看似不同的主题联系起来：对称和多位点修饰。我们研究了涉及单独或共同酶的底物的不同类别的随机修饰网络。我们证明，在修饰网络的不同对称实例下（显式或隐式调用，并在文献中讨论），多位点修饰的生物化学可以导致对称性被打破。这在计算上进行了演示，并通过分析进行了巩固，揭示了对称性被打破的参数区域，以及对称性被打破的状态的特征。我们讨论了在不存在精确对称性的情况下这些结果的相关性。总的来说，通过我们的研究，我们展示了对称性破坏如何（i）可以赋予蛋白质网络新的功能，包括不同物种组合的浓度鲁棒性（与多个稳定状态相结合）；（ii）可能是广泛存在于细胞中的多位点修饰排序的基础；（iii）可以显著影响多位点修饰和细胞信号转导网络/途径中的信息处理，其中存在多位点修饰；（iv）可以成为合成生物学和化学工程中的一个有前途的新角度。总的来说，新兴的概念综合为阐明和工程化学和生物系统交界处的分子系统提供了一个新的视角。
