Understanding apparent DNA flexibility enhancement by HU and HMGB architectural proteins.
Understanding apparent DNA flexibility enhancement by HU and HMGB architectural proteins.
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DOI：
10.1016/j.jmb.2011.03.050
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发表时间：
2011-06-03
影响因子：
5.6
通讯作者：
Maher LJ 3rd
中科院分区：
文献类型：
--
作者：
Czapla L;Peters JP;Rueter EM;Olson WK;Maher LJ 3rd
理解和预测蛋白质/DNA复合物的力学性质是生物物理学中具有挑战性的问题。某些结构蛋白结合DNA没有序列特异性，并强烈扭曲双螺旋。这些蛋白质快速结合和解结合，似乎增强了DNA的灵活性，如环化动力学所测量的。结构蛋白克服DNA刚性的能力具有重要的生物学意义，但这些蛋白增强DNA柔性的详细机制尚不清楚。在这里，我们采用了一种新的蒙特-卡罗方法，结合蛋白质对DNA结构的精确影响，以解释细菌组蛋白样HU蛋白和两个真核高迁移率族B类（HMGB）蛋白结合~200 bp的DNA分子的新的实验数据。这些数据（实验测量的蛋白质诱导的DNA环化的增加）与模拟的环化倾向进行比较，以推断封闭的蛋白质/DNA组件的全局结构和结合特性。模拟解释了所有观察到的（链长和浓度依赖性）蛋白质对DNA行为的影响，包括在DNA长度不是完整的螺旋重复序列时观察到的实验环化最大值如何反映了结构蛋白质对DNA的变形，以及不同蛋白质对DNA的随机结合如何将DNA环化增强到不同水平。这种实验和模拟的结合提供了一种强有力的新方法来解决蛋白质/DNA相互作用的生物物理学中的一个长期存在的问题。
Understanding and predicting the mechanical properties of protein/DNA complexes are challenging problems in biophysics. Certain architectural proteins bind DNA without sequence specificity and strongly distort the double helix. These proteins rapidly bind and unbind, seemingly enhancing the flexibility of DNA as measured by cyclization kinetics. The ability of architectural proteins to overcome DNA stiffness has important biological consequences, but the detailed mechanism of apparent DNA flexibility enhancement by these proteins has not been clear. Here we apply a novel Monte-Carlo approach that incorporates the precise effects of protein on DNA structure to interpret new experimental data for the bacterial histone-like HU protein and two eukaryotic high mobility group class B (HMGB) proteins binding to ~200-bp DNA molecules. These data (experimental measurement of protein-induced increase in DNA cyclization) are compared with simulated cyclization propensities to deduce the global structure and binding characteristics of the closed protein/DNA assemblies. The simulations account for all observed (chain-length and concentration-dependent) effects of protein on DNA behavior, including how the experimental cyclization maxima, observed at DNA lengths that are not an integral helical repeat, reflect the deformation of DNA by the architectural proteins and how random DNA binding by different proteins enhances DNA cyclization to different levels. This combination of experiment and simulation provides a powerful new approach to resolve a longstanding problem in the biophysics of protein/DNA interactions.
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