Structural and thermodynamic strategies for site-specific DNA binding proteins
Structural and thermodynamic strategies for site-specific DNA binding proteins
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DOI：
10.1016/s0969-2126(00)00501-3
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发表时间：
2000-10-15
期刊：
影响因子：
5.7
通讯作者：
Jacobson, LA
中科院分区：
文献类型：
--
作者：
Jen-Jacobson, L;Engler, LE;Jacobson, LA
背景资料：位点特异性蛋白质-DNA复合物在结构性质和热力学策略上差异很大，以达到适当的结合自由能。更好地理解的结构和充满活力的工程原理可能会导致合理的方法修改或设计这样的protein.Results：一种新的分析10个特定位点的蛋白质-DNA复合物揭示了一个惊人的对应关系的程度施加的DNA畸变和热力学参数的每个系统。对于具有相对未扭曲的DNA的复合物，有利的焓变驱动不利的熵变，而对于具有高度扭曲的DNA的复合物，不利的DeltaH度由有利的DeltaS度驱动。我们第一次表明，蛋白质-DNA协会有等温熵补偿，不同于温度依赖性补偿，所以DeltaH度和DeltaS度不独立变化。所有复合物都具有来自直接蛋白质-DNA识别相互作用的有利DeltaH度和来自水释放的有利DeltaS度。然而，强烈扭曲DNA的系统由于分子应变而具有净不利的DeltaH度，主要与碱基对去堆积有关。这些系统几乎没有偶联蛋白质折叠，并且应变界面受到的固定较少，因此DeltaS度是净有利的。相比之下，DNA畸变很少的系统具有净有利的DeltaH度，其必须被来自振动熵损失的净不利DeltaS度抵消（等温熵-熵补偿的结果）以及DNA结合和蛋白质折叠之间的耦合。等温熵-熵补偿意味着结构最优，非应变配合仅以熵上不利的固定为代价来实现，而熵上较弱的应变界面需要较小的熵损失。
Background: Site-specific protein-DNA complexes vary greatly in structural properties and in the thermodynamic strategy far achieving an appropriate binding free energy. A better understanding of the structural and energetic engineering principles might lead to rational methods for modification or design of such proteins.Results: A novel analysis of ten site-specific protein-DNA complexes reveals a striking correspondence between the degree of imposed DNA distortion and the thermodynamic parameters of each system. For complexes with relatively undistorted DNA, favorable enthalpy change drives unfavorable entropy change, whereas for complexes with highly distorted DNA, unfavorable DeltaH degrees is driven by favorable DeltaS degrees. We show for the first time that protein-DNA associations have isothermal enthalpy-entropy compensation, distinct from temperature-dependent compensation, so DeltaH degrees and DeltaS degrees do not vary independently. All complexes have favorable DeltaH degrees from direct protein-DNA recognition interactions and favorable DeltaS degrees from water release. Systems that strongly distort the DNA nevertheless have net unfavorable DeltaH degrees as the result of molecular strain, primarily associated with the base pair destacking. These systems have little coupled protein folding and the strained interface suffers less immobilization, so DeltaS degrees is net favorable. By contrast, systems with little DNA distortion have net favorable DeltaH degrees, which must be counterbalanced by net unfavorable DeltaS degrees, derived from loss of vibrational entropy (a result of isothermal enthalpy-entropy compensation) and from coupling between DNA binding and protein folding.Conclusions: Isothermal enthalpy-entropy compensation implies that a structurally optimal, unstrained fit is achieved only at the cost of entropically unfavorable immobilization, whereas an enthalpically weaker, strained interface entails smaller entropic penalties.