Dynamic Strategies for Target-Site Search by DNA-Binding Proteins
Dynamic Strategies for Target-Site Search by DNA-Binding Proteins
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DOI：
10.1016/j.bpj.2010.02.055
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发表时间：
2010-06-16
影响因子：
3.4
通讯作者：
Spakowitz, Andrew J.
中科院分区：
文献类型：
--
作者：
de la Rosa, Mario A. Diaz;Koslover, Elena F.;Spakowitz, Andrew J.
基因调控蛋白在DNA上非常迅速地找到它们的靶位点;乳糖阻遏物的实验结合率比单独通过自由扩散预测的高出几个数量级。有人提出，非特异性结合通过允许蛋白质沿着DNA滑动和沿着跳跃来帮助搜索。我们开发了蛋白质移位的反应扩散理论，该理论解释了链上和链外的运输，并结合了DNA的物理构象。对于线性DNA的蠕虫状链模型，啤酒花的分布可用于蛋白质展示长，幂律尾巴，使长时间的位移沿着链超扩散。我们的分析预测有效的超扩散系数为给定的非特异性结合和解离速率参数。反式定位率表现出最大的结合速率常数的中间值，而搜索效率优化在较大的结合速率常数值。因此，我们的理论预测了一个区域的非特异性结合和未结合率参数的值，平衡蛋白质易位率和搜索的效率。几种蛋白质的已发表数据福尔斯落在该参数值的预测区域内。
Gene regulatory proteins find their target sites on DNA remarkably quickly; the experimental binding rate for lac repressor is orders-of-magnitude higher than predicted by free diffusion alone. It has been proposed that nonspecific binding aids the search by allowing proteins to slide and hop along DNA. We develop a reaction-diffusion theory of protein translocation that accounts for transport both on and off the strand and incorporates the physical conformation of DNA. For linear DNA modeled as a wormlike chain, the distribution of hops available to a protein exhibits long, power-law tails that make the long-time displacement along the strand superdiffusive. Our analysis predicts effective superdiffusion coefficients for given nonspecific binding and unbinding rate parameters. Trans location rate exhibits a maximum at intermediate values of the binding rate constant, while search efficiency is optimized at larger binding rate constant values. Thus, our theory predicts a region of values of the nonspecific binding and unbinding rate parameters that balance the protein translocation rate and the efficiency of the search. Published data for several proteins falls within this predicted region of parameter values.