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单分子可作为原始的生物传感器、开关和振荡器。

Single molecules can operate as primitive biological sensors, switches and oscillators.

作者信息

Hernansaiz-Ballesteros Rosa D, Cardelli Luca, Csikász-Nagy Attila

机构信息

Randall Centre for Cell and Molecular Biophysics and Institute for Mathematical and Molecular Biomedicine, King's College London, London, SE1 1UL, UK.

Microsoft Research, 21 Station Road, Cambridge, CB1 2FB, UK.

出版信息

BMC Syst Biol. 2018 Jun 18;12(1):70. doi: 10.1186/s12918-018-0596-4.

Abstract

BACKGROUND

Switch-like and oscillatory dynamical systems are widely observed in biology. We investigate the simplest biological switch that is composed of a single molecule that can be autocatalytically converted between two opposing activity forms. We test how this simple network can keep its switching behaviour under perturbations in the system.

RESULTS

We show that this molecule can work as a robust bistable system, even for alterations in the reactions that drive the switching between various conformations. We propose that this single molecule system could work as a primitive biological sensor and show by steady state analysis of a mathematical model of the system that it could switch between possible states for changes in environmental signals. Particularly, we show that a single molecule phosphorylation-dephosphorylation switch could work as a nucleotide or energy sensor. We also notice that a given set of reductions in the reaction network can lead to the emergence of oscillatory behaviour.

CONCLUSIONS

We propose that evolution could have converted this switch into a single molecule oscillator, which could have been used as a primitive timekeeper. We discuss how the structure of the simplest known circadian clock regulatory system, found in cyanobacteria, resembles the proposed single molecule oscillator. Besides, we speculate if such minimal systems could have existed in an RNA world.

摘要

背景

开关式和振荡式动力系统在生物学中广泛存在。我们研究了由单个分子构成的最简单的生物开关,该分子能够在两种相反的活性形式之间进行自催化转化。我们测试了这个简单网络在系统受到扰动时如何保持其开关行为。

结果

我们表明,即使驱动各种构象之间转换的反应发生改变,该分子仍可作为一个稳健的双稳态系统发挥作用。我们提出,这个单分子系统可以作为一种原始的生物传感器,并通过对该系统数学模型的稳态分析表明,它可以因环境信号的变化而在不同状态之间切换。特别地,我们表明单分子磷酸化 - 去磷酸化开关可以作为核苷酸或能量传感器。我们还注意到,反应网络中特定的一组简化可能会导致振荡行为的出现。

结论

我们提出,进化可能已将这个开关转化为一个单分子振荡器,它可能曾被用作原始的计时装置。我们讨论了在蓝细菌中发现的最简单的已知昼夜节律时钟调节系统的结构如何类似于所提出的单分子振荡器。此外,我们推测在RNA世界中是否可能存在这样的最小系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c219/6007071/dc1f2d8db5bd/12918_2018_596_Fig1_HTML.jpg

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