Proofreading through spatial gradients.
Proofreading through spatial gradients.
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DOI：
10.7554/elife.60415
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发表时间：
2020-12-24
期刊：
影响因子：
7.7
通讯作者：
Phillips R
中科院分区：
文献类型：
--
作者：
Galstyan V;Husain K;Xiao F;Murugan A;Phillips R
关键的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。然而，传统校对方案的适用性是有限的，因为它们通常需要酶中的专用结构特征，例如核苷酸水解位点或多个中间构象。在这里，我们探讨了一种替代的概念机制，实现错误校正的基板绑定和随后的产品形成发生在不同的物理位置。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。这种机构没有典型的结构要求，在实验中容易被忽略。我们讨论了分子梯度的长度尺度如何决定校对性能，并量化了现实的扩散和反应速率所施加的限制。我们的工作拓宽了动力学校对的适用性，并为研究空间梯度作为实现特异性的可能途径奠定了基础。
Key enzymatic processes use the nonequilibrium error correction mechanism called kinetic proofreading to enhance their specificity. The applicability of traditional proofreading schemes, however, is limited because they typically require dedicated structural features in the enzyme, such as a nucleotide hydrolysis site or multiple intermediate conformations. Here, we explore an alternative conceptual mechanism that achieves error correction by having substrate binding and subsequent product formation 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 have the typical structural requirements, making it easier to overlook in experiments. We discuss how the length scales of molecular gradients dictate proofreading performance, and quantify the limitations imposed by realistic diffusion and reaction rates. Our work broadens the applicability of kinetic proofreading and sets the stage for studying spatial gradients as a possible route to specificity.