Pabo C O, Sauer R T
Annu Rev Biochem. 1984;53:293-321. doi: 10.1146/annurev.bi.53.070184.001453.
Several general principles emerge from the studies of Cro, lambda repressor, and CAP. The DNA-binding sites are recognized in a form similar to B-DNA. They do not form cruciforms or other novel DNA structures. There seem to be proteins that bind left-handed Z-DNA (87) and DNA in other conformations, but it remains to be seen how these structures are recognized or how proteins recognize specific sequences in single-stranded DNA. Cro, repressor, and CAP use symmetrically related subunits to interact with two-fold related sites in the operator sequences. Many other DNA-binding proteins are dimers or tetramers and their operator sequences have approximate two-fold symmetry. It seems likely that these proteins will, like Cro, repressor, and CAP, form symmetric complexes. However, there is no requirement for symmetry in protein-DNA interactions. Some sequence-specific DNA-binding proteins, like RNA polymerase, do not have symmetrically related subunits and do not bind to symmetric recognition sequences. Cro, repressor, and CAP use alpha-helices for many of the contacts between side chains and bases in the major groove. An adjacent alpha-helical region contacts the DNA backbone and may help to orient the "recognition" helices. This use of alpha-helical regions for DNA binding appears to be a common mode of recognition. Most of the contacts made by Cro, repressor, and CAP occur on one side of the double helix. However, lambda repressor contacts both sides of the double helix by using a flexible region of protein to wrap around the DNA. Recognition of specific base sequences involves hydrogen bonds and van der Waals interactions between side chains and the edges of base pairs. These specific interactions, together with backbone interactions and electrostatic interactions, stabilize the protein-DNA complexes. The current models for the complexes of Cro, repressor, and CAP with operator DNA are probably fundamentally correct, but it should be emphasized that model building alone, even when coupled with genetic and biochemical studies, cannot be expected to provide a completely reliable "high-resolution" view of the protein-DNA complex. For example, the use of standard B-DNA geometry for the operator is clearly an approximation.(ABSTRACT TRUNCATED AT 400 WORDS)
对Cro蛋白、λ阻遏蛋白和CAP的研究得出了几个普遍原则。DNA结合位点是以类似于B-DNA的形式被识别的。它们不会形成十字形或其他新颖的DNA结构。似乎存在能结合左手Z-DNA（87）及其他构象DNA的蛋白质，但这些结构如何被识别以及蛋白质如何识别单链DNA中的特定序列仍有待观察。Cro蛋白、阻遏蛋白和CAP利用对称相关的亚基与操纵基因序列中具有双重对称性的位点相互作用。许多其他DNA结合蛋白是二聚体或四聚体，它们的操纵基因序列具有近似的双重对称性。这些蛋白质似乎很可能会像Cro蛋白、阻遏蛋白和CAP一样形成对称复合物。然而，蛋白质与DNA的相互作用并不一定需要对称性。一些序列特异性DNA结合蛋白，如RNA聚合酶，没有对称相关的亚基，也不与对称的识别序列结合。Cro蛋白、阻遏蛋白和CAP在许多情况下利用α螺旋来实现侧链与大沟中碱基之间的接触。相邻的α螺旋区域与DNA主链接触，可能有助于使“识别”螺旋定向。利用α螺旋区域进行DNA结合似乎是一种常见的识别方式。Cro蛋白、阻遏蛋白和CAP形成的大多数接触发生在双螺旋的一侧。然而，λ阻遏蛋白通过利用蛋白质的一个柔性区域环绕DNA来与双螺旋的两侧接触。对特定碱基序列的识别涉及侧链与碱基对边缘之间的氢键和范德华相互作用。这些特定相互作用，连同主链相互作用和静电相互作用，稳定了蛋白质 - DNA复合物。目前关于Cro蛋白、阻遏蛋白和CAP与操纵基因DNA复合物的模型可能在根本上是正确的，但应该强调的是，仅靠模型构建，即使与遗传学和生物化学研究相结合，也不能期望提供蛋白质 - DNA复合物完全可靠的“高分辨率”视图。例如，将操纵基因使用标准B-DNA几何结构显然是一种近似。（摘要截选至400字）
