Unlimited multistability and Boolean logic in microbial signalling.
Unlimited multistability and Boolean logic in microbial signalling.
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DOI：
10.1098/rsif.2015.0234
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发表时间：
2015-07-06
期刊：
影响因子：
--
通讯作者：
Soyer OS
中科院分区：
文献类型：
--
作者：
Kothamachu VB;Feliu E;Cardelli L;Soyer OS
将环境信号映射到不同的内部生理状态或程序的能力对单细胞微生物至关重要。支撑这种能力的一个关键系统动力学特征是多稳定性。虽然已知无限的多稳定性是由真核细胞信号网络中的多位点磷酸化引起的，但在微生物信号系统中还没有发现类似的通用机制。这些系统通常被称为双组分系统，其包含组氨酸激酶（HK）受体和参与磷酸转移反应的应答调节蛋白。我们开发了一个数学框架，用于分析微生物系统与多域HK受体被称为混合和非正统HK。我们发现，这些系统嵌入了一个简单的核心网络，表现出多稳态，从而揭示了一种新的生化机制的多稳态。我们进一步证明，共享的下游组件允许一个系统与n多域混合HK达到3n稳态。我们发现，这样的系统，当感测不同的信号，可以很容易地实现这些信号的布尔逻辑功能。使用两个实验研究的例子，两个组件系统实现混合香港，我们表明，双稳态和逻辑功能的实现是可能的生物学上可行的反应速率。此外，我们发现，所有测序的微生物基因组包含大量的混合和非正统的香港，和一些基因组有更大的比例，这些蛋白质相比，定期香港。因此，微生物细胞在将不同的环境信号映射到不同的生理状态并对其进行复杂计算方面理论上是无限的。这些发现促进了对天然双组分系统的理解，并允许通过合成生物学对其进行工程改造。
The ability to map environmental signals onto distinct internal physiological states or programmes is critical for single-celled microbes. A crucial systems dynamics feature underpinning such ability is multistability. While unlimited multistability is known to arise from multi-site phosphorylation seen in the signalling networks of eukaryotic cells, a similarly universal mechanism has not been identified in microbial signalling systems. These systems are generally known as two-component systems comprising histidine kinase (HK) receptors and response regulator proteins engaging in phosphotransfer reactions. We develop a mathematical framework for analysing microbial systems with multi-domain HK receptors known as hybrid and unorthodox HKs. We show that these systems embed a simple core network that exhibits multistability, thereby unveiling a novel biochemical mechanism for multistability. We further prove that sharing of downstream components allows a system with n multi-domain hybrid HKs to attain 3n steady states. We find that such systems, when sensing distinct signals, can readily implement Boolean logic functions on these signals. Using two experimentally studied examples of two-component systems implementing hybrid HKs, we show that bistability and implementation of logic functions are possible under biologically feasible reaction rates. Furthermore, we show that all sequenced microbial genomes contain significant numbers of hybrid and unorthodox HKs, and some genomes have a larger fraction of these proteins compared with regular HKs. Microbial cells are thus theoretically unbounded in mapping distinct environmental signals onto distinct physiological states and perform complex computations on them. These findings facilitate the understanding of natural two-component systems and allow their engineering through synthetic biology.
影响因子：
4.3
作者：
Hoyle RB;Avitabile D;Kierzek AM
通讯作者：
Kierzek AM