High resolution structural studies of Cro repressor protein and implications for DNA recognition.
High resolution structural studies of Cro repressor protein and implications for DNA recognition.
复制标题
Cro 阻遏蛋白的高分辨率结构研究及其对 DNA 识别的影响。
DOI：
10.1080/07391102.1983.10507461
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发表时间：
1983
影响因子：
4.4
通讯作者：
Matthews,BW
中科院分区：
文献类型：
--
作者：
Ohlendorf,DH;Anderson,WF;Takeda,Y;Matthews,BW
Cro阻遏物是一种小的二聚体蛋白，与λ噬菌体DNA上的特定位点结合。Cro的结构已被确定，并表明该蛋白质与其序列特异性位点结合，该蛋白质的一对双重相关的α-螺旋位于DNA的连续主要沟内。从已知的阻遏物的三维结构，模型建立和能量精化已被用于开发Cro和DNA之间的假定复合物的详细模型。特异性DNA结合位点的识别似乎是通过蛋白质的氨基酸侧链和DNA大沟内暴露的碱基对原子之间的多个氢键发生的。Cro：DNA模型与计算的蛋白质静电势能面一致。从一系列氨基酸序列和基因序列的比较来看，似乎许多其他DNA结合蛋白具有与Cro中所见相似的α螺旋DNA结合区。表观序列同源性不仅包括来自不同噬菌体的DNA结合蛋白，还包括来自细菌和酵母的基因调控蛋白。Cro阻遏蛋白、λ阻遏蛋白和CAP基因激活蛋白的部分DNA结合区的构象也非常相似。总之，这些结果强烈表明，一个双螺旋结构单元发生在许多蛋白质的DNA结合区，调节基因表达。然而，迄今为止的结果并不表明氨基酸和碱基之间存在简单的一对一识别码。已经获得了Cro与六碱基对和九碱基对DNA寡聚体的复合物的晶体，并且这些共晶体的X射线分析正在进行中。
Cro repressor is a small dimeric protein that binds to specific sites on the DNA of bacteriophage λ. The structure of Cro has been determined and suggests that the protein binds to its sequence-specific sites with a pair of two-fold related α-helices of the protein located within successive major grooves of the DNA.From the known three-dimensional structure of the repressor, model building and energy refinement have been used to develop a detailed model for the presumed complex between Cro and DNA. Recognition of specific DNA binding sites appears to occur via multiple hydrogen bonds between amino acid side chains of the protein and base pair atoms exposed within the major groove of DNA. The Cro:DNA model is consistent with the calculated electrostatic potential energy surface of the protein.From a series of amino acid sequence and gene sequence comparisons, it appears that a number of other DNA-binding proteins have an α-helical DNA-binding region similar to that seen in Cro. The apparent sequence homology includes not only DNA-binding proteins from different bacteriophages, but also gene-regulatory proteins from bacteria and yeast. It has also been found that the conformations of part of the presumed DNA-binding regions of Cro repressor, λ repressor and CAP gene activator proteins are strikingly similar. Taken together, these results strongly suggest that a two-helical structural unit occurs in the DNA-binding region of many proteins that regulate gene expression. However, the results to date do not suggest that there is a simple one-to-one recognition code between amino acids and bases.Crystals have been obtained of complexes of Cro with six-base-pair and nine-basepair DNA oligomers, and X-ray analysis of these co-crystals is in progress.