竞争性抑制可使剂量反应线性化并产生线性整流器。
Competitive inhibition can linearize dose-response and generate a linear rectifier.
作者信息
Savir Yonatan, Tu Benjamin P, Springer Michael
机构信息
Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390.
出版信息
Cell Syst. 2015 Sep 23;1(3):238-245. doi: 10.1016/j.cels.2015.09.001.
Many biological responses require a dynamic range that is larger than standard bi-molecular interactions allow, yet the also ability to remain off at low input. Here we mathematically show that an enzyme reaction system involving a combination of competitive inhibition, conservation of the total level of substrate and inhibitor, and positive feedback can behave like a linear rectifier-that is, a network motif with an input-output relationship that is linearly sensitive to substrate above a threshold but unresponsive below the threshold. We propose that the evolutionarily conserved yeast SAGA histone acetylation complex may possess the proper physiological response characteristics and molecular interactions needed to perform as a linear rectifier, and we suggest potential experiments to test this hypothesis. One implication of this work is that linear responses and linear rectifiers might be easier to evolve or synthetically construct than is currently appreciated.
许多生物反应所需的动态范围大于标准双分子相互作用所能允许的范围，然而在低输入时也需要保持关闭状态的能力。在此，我们通过数学证明，一个涉及竞争性抑制、底物和抑制剂总量守恒以及正反馈相结合的酶反应系统，其行为可以像一个线性整流器——也就是说，是一种具有输入-输出关系的网络基序，在阈值以上对底物呈线性敏感，而在阈值以下无反应。我们提出，进化上保守的酵母SAGA组蛋白乙酰化复合物可能具备作为线性整流器发挥作用所需的适当生理反应特性和分子相互作用，并且我们建议了一些潜在实验来检验这一假设。这项工作的一个意义在于，线性响应和线性整流器可能比目前所认为的更容易进化或人工构建。
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