通过空间梯度进行校对
Proofreading through spatial gradients
摘要：
生物学中的关键酶过程使用称为动力学校正的非平衡误差校正机制来增强其特异性。动力学校正通常需要酶中的几个专用结构特征，例如核苷酸水解位点和延迟产物形成的多种酶-底物构象。这些要求限制了传统校对方案的适用性和适应性。在这里，我们探讨了一种替代的概念性纠错机制，通过使这些事件发生在不同的物理位置，实现了底物结合和随后的产物形成之间的延迟。利用酶-底物复合物从一个位置扩散到另一个位置所花费的时间来丢弃错误的底物。这种机制不需要酶上的专用结构元件，使其在实验中更容易被忽略，但也使校对在飞行中可调。我们讨论了如何调整酶或底物浓度梯度的长度尺度改变保真度，速度和能量耗散，并量化的性能限制所施加的现实扩散和反应速率在细胞中。我们的工作拓宽了动力学校对的适用性，并设置了空间梯度的研究作为一个可能的途径特异性的阶段。
英文摘要：
Key enzymatic processes in biology use the nonequilibrium error correction mechanism called kinetic proofreading to enhance their specificity. Kinetic proofreading typically requires several dedicated structural features in the enzyme, such as a nucleotide hydrolysis site and multiple enzyme-substrate conformations that delay product formation. Such requirements limit the applicability and the adaptability of traditional proofreading schemes. Here, we explore an alternative conceptual mechanism of error correction that achieves delays between substrate binding and subsequent product formation by having these events occur at distinct physical locations. The time taken by the enzyme-substrate complex to diffuse from one location to another is leveraged to discard wrong substrates. This mechanism does not require dedicated structural elements on the enzyme, making it easier to overlook in experiments but also making proofreading tunable on the fly. We discuss how tuning the length scales of enzyme or substrate concentration gradients changes the fidelity, speed and energy dissipation, and quantify the performance limitations imposed by realistic diffusion and reaction rates in the cell. Our work broadens the applicability of kinetic proofreading, and sets the stage for the study of spatial gradients as a possible route to specificity.
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