IMPORTANCE OF DNA STIFFNESS IN PROTEIN DNA-BINDING SPECIFICITY
IMPORTANCE OF DNA STIFFNESS IN PROTEIN DNA-BINDING SPECIFICITY
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DOI：
10.1038/329263a0
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发表时间：
1987-09-17
期刊：
影响因子：
64.8
通讯作者：
AUSTIN, RH
中科院分区：
文献类型：
--
作者：
HOGAN, ME;AUSTIN, RH
从第一个与其DNA识别序列特异性结合的阻遏物的高分辨率结构中，已经表明噬菌体434阻遏蛋白作为二聚体与螺旋结合。在结合位点的末端产生紧密的局部相互作用，导致中心的四个碱基对（bp）变得弯曲和过度扭曲。操纵子的中心不与蛋白质接触，但阻遏物结合亲和力可响应于其序列变化而降低至少50倍2。这一观察结果可以解释的干预DNA片段的结构随其序列而变化，或者如果DNA在中心的运营商抵制扭转和弯曲变形所需的复杂的形成在一个序列依赖的方式。我们已经考虑了第二个假设，证明DNA刚度是序列依赖性的。一种方法，制定用于计算任何特定的DNA序列的刚度，我们表明，这种预测的序列和刚度之间的关系可以解释阻遏物结合数据的定量方式。我们建议，DNA的弹性性质可能是普遍的重要性，以了解蛋白质-DNA结合特异性。
From the first high-resolution structure of a repressor bound specifically to its DNA recognition sequence1it has been shown that the phage 434 repressor protein binds as a dimer to the helix. Tight, local interactions are made at the ends of the binding site, causing the central four base pairs (bp) to become bent and overtwisted. The centre of the operator is not in contact with protein but repressor binding affinity can be reduced at least 50-fold in response to a sequence change there2. This observation might be explained should the structure of the intervening DNA segment vary with its sequence, or if DNA at the centre of the operator resists the torsional and bending deformation necessary for complex formation in a sequence dependent fashion. We have considered the second hypothesis by demonstrating that DNA stiffness is sequence dependent. A method is formulated for calculating the stiffness of any particular DNA sequence, and we show that this predicted relationship between sequence and stiffness can explain the repressor binding data in a quantitative manner. We propose that the elastic properties of DNA may be of general importance to an understanding of protein–DNA binding specificity.