Department of Mathematical Informatics, Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan and Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-Ku, Tokyo 153-8505, Japan.
Phys Rev E. 2017 Jul;96(1-1):012405. doi: 10.1103/PhysRevE.96.012405. Epub 2017 Jul 14.
Specific interactions between receptors and their target ligands in the presence of nontarget ligands are crucial for biological processes such as T cell ligand discrimination. To discriminate between the target and nontarget ligands, cells have to increase specificity to the target ligands by amplifying the small differences in affinity among ligands. In addition, sensitivity to the ligand concentration and quick discrimination are also important to detect low amounts of target ligands and facilitate fast cellular decision making after ligand recognition. In this work we propose a mechanism for nonlinear specificity amplification (ultraspecificity) based on zero-order saturating reactions, which was originally proposed to explain nonlinear sensitivity amplification (ultrasensitivity) to the ligand concentration. In contrast to the previously proposed proofreading mechanisms that amplify the specificity by a multistep reaction, our model can produce an optimal balance of specificity, sensitivity, and quick discrimination. Furthermore, we show that a model for insensitivity to a large number of nontarget ligands can be naturally derived from a model with the zero-order ultraspecificity. The zero-order ultraspecificity, therefore, may provide an alternative way to understand ligand discrimination from the viewpoint of nonlinear properties in biochemical reactions.
特定受体与其靶标配体之间的相互作用，在存在非靶标配体的情况下，对于 T 细胞配体识别等生物过程至关重要。为了区分靶标和非靶标配体，细胞必须通过放大配体之间亲和力的微小差异来提高对靶标配体的特异性。此外，对配体浓度的敏感性和快速区分对于检测低浓度的靶标配体以及在配体识别后促进快速的细胞决策也很重要。在这项工作中，我们提出了一种基于零级饱和反应的非线性特异性放大（超特异性）的机制，该机制最初是为了解释对配体浓度的非线性敏感性放大（超敏感性）而提出的。与以前提出的通过多步反应放大特异性的校对机制不同，我们的模型可以在特异性、敏感性和快速区分之间达到最佳平衡。此外，我们还表明，一种对大量非靶标配体不敏感的模型可以从具有零级超特异性的模型中自然推导出。因此，零级超特异性可能为从生化反应的非线性特性角度理解配体识别提供了一种替代方法。
