Várnai Péter, Djuranovic Dragana, Lavery Richard, Hartmann Brigitte
Laboratoire de Biochimie Théorique, CNRS UPR 9080, Institut de Biologie Physico-Chimique, 13 Rue Pierre et Marie Curie, Paris 75005, France.
Nucleic Acids Res. 2002 Dec 15;30(24):5398-406. doi: 10.1093/nar/gkf680.
In the crystal structures of protein complexes with B-DNA, alpha and gamma DNA backbone torsion angles often exhibit non-canonical values. It is not known if these alternative backbone conformations are easily accessible in solution and can contribute to the specific recognition of DNA by proteins. We have analysed the coupled transition of the alpha and gamma torsion angles within the central GpC step of a B-DNA dodecamer by computer simulations. Five stable or metastable non-canonical alpha/gamma sub-states are found. The most favourable pathway from the canonical alpha/gamma structure to any unusual form involves a counter-rotation of alpha and gamma, via the trans conformation. However, the corresponding free energy indicates that spontaneous flipping of the torsions is improbable in free B-DNA. This is supported by an analysis of the available high resolution crystallographic structures showing that unusual alpha/gamma states are only encountered in B-DNA complexed to proteins. An analysis of the structural consequences of alpha/gamma transitions shows that the non-canonical backbone geometry influences essentially the roll and twist values and reduces the equilibrium dispersion of structural parameters. Our results support the hypothesis that unusual alpha/gamma backbones arise during protein-DNA complexation, assisting the fine structural adjustments between the two partners and playing a role in the overall complexation free energy.
在与B型DNA形成的蛋白质复合物的晶体结构中，α和γ DNA主链扭转角常常呈现非标准值。尚不清楚这些非标准的主链构象在溶液中是否易于形成，以及是否有助于蛋白质对DNA的特异性识别。我们通过计算机模拟分析了B型DNA十二聚体中心GpC步内α和γ扭转角的耦合转变。发现了五个稳定或亚稳定的非标准α/γ亚状态。从标准α/γ结构转变为任何异常形式的最有利途径是通过反式构象使α和γ发生反向旋转。然而，相应的自由能表明，在游离的B型DNA中，扭转自发翻转的可能性不大。对现有高分辨率晶体结构的分析支持了这一点，该分析表明，只有在与蛋白质复合的B型DNA中才会遇到异常的α/γ状态。对α/γ转变的结构后果的分析表明，非标准的主链几何结构主要影响滚动和扭转值，并减少结构参数的平衡离散度。我们的结果支持这样一种假设，即异常的α/γ主链是在蛋白质-DNA复合过程中产生的，有助于两个结合伙伴之间进行精细的结构调整，并在整个复合自由能中发挥作用。
