Cooperative stability renders protein complex formation more robust and controllable.
Cooperative stability renders protein complex formation more robust and controllable.
复制标题
协同稳定性使蛋白质复合物的形成更加稳健和可控。
DOI：
10.1038/s41598-022-14362-z
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发表时间：
2022-06-21
影响因子：
4.6
通讯作者：
Yeang, Chen-Hsiang
中科院分区：
文献类型：
--
作者：
Hsu, Kuan-Lun;Yen, Hsueh-Chi S.;Yeang, Chen-Hsiang
蛋白质复合物是许多生物功能的基本单位。尽管它们有许多优点，但蛋白质复合物的一个主要不利影响是未组装亚基的积累，可能会破坏其他过程或发挥细胞毒性作用。过量亚基的合成可以通过负反馈控制来抑制，或者它们可以比组装的亚基更有效地降解，后者被称为合作稳定性。虽然复杂亚基的受控合成已经被广泛研究，但在复杂的地层中，协同稳定性是如何起作用的，这在很大程度上仍未被探索。为了填补这一知识空白，我们建立了具有或不具有合作稳定性的异质配合物的定量模型，并比较了它们在合成速率变化下的行为。具有协同稳定性的体系对合成速率变化具有较强的稳定性，因为它在很宽的参数配置范围内保持较高的二聚体/单体比例。此外，合作稳定性可以缓解给定亚基供应有限的约束，使复杂丰度对另一个亚基的单边上调更敏感。我们还进行了一项计算机实验，以全面表征和比较四种类型的电路，这些电路结合了负反馈控制和合作稳定性的组合，涉及与最优性、鲁棒性和可控性相关的八个系统特征。有趣的是，尽管单个电路具有不同的特性，但仅具有合作稳定性的系统在所有特性中实现了最平衡的性能。我们的研究为合作稳定性对自然生物系统的贡献提供了理论依据，并为设计具有理想特性的合成复杂地层系统提供了指导方针。
Protein complexes are the fundamental units of many biological functions. Despite their many advantages, one major adverse impact of protein complexes is accumulations of unassembled subunits that may disrupt other processes or exert cytotoxic effects. Synthesis of excess subunits can be inhibited via negative feedback control or they can be degraded more efficiently than assembled subunits, with this latter being termed cooperative stability. Whereas controlled synthesis of complex subunits has been investigated extensively, how cooperative stability acts in complex formation remains largely unexplored. To fill this knowledge gap, we have built quantitative models of heteromeric complexes with or without cooperative stability and compared their behaviours in the presence of synthesis rate variations. A system displaying cooperative stability is robust against synthesis rate variations as it retains high dimer/monomer ratios across a broad range of parameter configurations. Moreover, cooperative stability can alleviate the constraint of limited supply of a given subunit and makes complex abundance more responsive to unilateral upregulation of another subunit. We also conducted an in silico experiment to comprehensively characterize and compare four types of circuits that incorporate combinations of negative feedback control and cooperative stability in terms of eight systems characteristics pertaining to optimality, robustness and controllability. Intriguingly, though individual circuits prevailed for distinct characteristics, the system with cooperative stability alone achieved the most balanced performance across all characteristics. Our study provides theoretical justification for the contribution of cooperative stability to natural biological systems and represents a guideline for designing synthetic complex formation systems with desirable characteristics.
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影响因子：
16
作者：
Lin HC;Yeh CW;Chen YF;Lee TT;Hsieh PY;Rusnac DV;Lin SY;Elledge SJ;Zheng N;Yen HS
通讯作者：
Yen HS
影响因子：
5.2
作者：
Cerychova R;Pavlinkova G
通讯作者：
Pavlinkova G
影响因子：
9.2
作者：
Lam, Yun Wah;Lamond, Angus I.;Mann, Matthias;Andersen, Jens S.
通讯作者：
Andersen, Jens S.
影响因子：
13.8
作者：
Dandekar, T;Snel, B;Bork, P
通讯作者：
Bork, P
影响因子：
5.6
作者：
Keeble, Anthony H.;Joachimiak, Lukasz A.;Kleanthous, Cohn
通讯作者：
Kleanthous, Cohn