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Proofreading through spatial gradients
bioRxiv - Biophysics Pub Date : 2020-05-24 , DOI: 10.1101/2020.05.23.112664
Vahe Galstyan , Kabir Husain , Fangzhou Xiao , Arvind Murugan , Rob Phillips

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.

中文翻译:

通过空间梯度校对

生物学中的关键酶促过程使用称为动力学校对的非平衡误差校正机制来增强其特异性。动力学校对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个酶-底物构象。这样的要求限制了传统校对方案的适用性和适应性。在这里,我们探索错误校正的另一种概念机制,该机制通过使这些事件发生在不同的物理位置来实现底物结合和后续产品形成之间的延迟。酶-底物复合物从一个位置扩散到另一位置所花费的时间被用来丢弃错误的底物。该机制不需要酶上的专用结构元件,因此更容易在实验中被忽略,而且还可以即时校正校对。我们讨论了如何调节酶或底物浓度梯度的长度尺度如何改变保真度,速度和能量耗散,并量化细胞中实际扩散和反应速率所施加的性能限制。我们的工作拓宽了动力学校对的适用范围,并为研究空间梯度奠定了基础,这是实现特异性的可能途径。并量化由实际扩散和反应速率在电池中施加的性能限制。我们的工作拓宽了动力学校对的适用范围,并为研究空间梯度奠定了基础,这是实现特异性的可能途径。并量化由实际扩散和反应速率在电池中施加的性能限制。我们的工作拓宽了动力学校对的适用范围,并为研究空间梯度奠定了基础,这是实现特异性的可能途径。
更新日期:2020-05-24
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