Generalized Facilitated Diffusion Model for DNA-Binding Proteins with Search and Recognition States
Generalized Facilitated Diffusion Model for DNA-Binding Proteins with Search and Recognition States
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DOI：
10.1016/j.bpj.2012.04.008
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发表时间：
2012-05-16
影响因子：
3.4
通讯作者：
Metzler, Ralf
中科院分区：
文献类型：
--
作者：
Bauer, Maximilian;Metzler, Ralf
转录因子（TFs）如lac抑制因子在DNA上找到目标序列的速率非常高。在该搜索过程的Berg-von Hippel模型中，TF在体溶液中的三维扩散和沿着DNA链的一维滑动之间交替。为了克服所谓的速度-稳定性悖论，在类似的模型中，TF被认为存在于两种构象（搜索状态和识别状态）中，并在两种构象之间随机切换。结合易扩散模型和交变状态模型，得到了一个广义模型。我们明确地处理平行排列的棒状链的大块漂移，并考虑一个简化的螺旋DNA模型。与先前考虑的便利扩散模型相比，对应于我们的广义模型的极限情况，我们令人惊讶地发现目标搜索率降低了。此外，在最佳条件下，蛋白质在DNA链上和链外所花费的时间不再是均分的。
Transcription factors (TFs) such as the lac repressor find their target sequence on DNA at remarkably high rates. In the established Berg-von Hippel model for this search process, the TF alternates between three-dimensional diffusion in the bulk solution and one-dimensional sliding along the DNA chain. To overcome the so-called speed-stability paradox, in similar models the TF was considered as being present in two conformations (search state and recognition state) between which it switches stochastically. Combining both the facilitated diffusion model and alternating states, we obtain a generalized model. We explicitly treat bulk excursions for rodlike chains arranged in parallel and consider a simplified model for coiled DNA. Compared to previously considered facilitated diffusion models, corresponding to limiting cases of our generalized model, we surprisingly find a reduced target search rate. Moreover, at optimal conditions there is no longer an equipartition between the time spent by the protein on and off the DNA chain.