Rozenberg H, Rabinovich D, Frolow F, Hegde R S, Shakked Z
Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15194-9. doi: 10.1073/pnas.95.26.15194.
Transcriptional regulation in papillomaviruses depends on sequence-specific binding of the regulatory protein E2 to several sites in the viral genome. Crystal structures of bovine papillomavirus E2 DNA targets reveal a conformational variant of B-DNA characterized by a roll-induced writhe and helical repeat of 10.5 bp per turn. A comparison between the free and the protein-bound DNA demonstrates that the intrinsic structure of the DNA regions contacted directly by the protein and the deformability of the DNA region that is not contacted by the protein are critical for sequence-specific protein/DNA recognition and hence for gene-regulatory signals in the viral system. We show that the selection of dinucleotide or longer segments with appropriate conformational characteristics, when positioned at correct intervals along the DNA helix, can constitute a structural code for DNA recognition by regulatory proteins. This structural code facilitates the formation of a complementary protein-DNA interface that can be further specified by hydrogen bonds and nonpolar interactions between the protein amino acids and the DNA bases.
乳头瘤病毒中的转录调控取决于调节蛋白E2与病毒基因组中多个位点的序列特异性结合。牛乳头瘤病毒E2 DNA靶标的晶体结构揭示了B-DNA的一种构象变体，其特征是由滚动诱导的扭曲和每圈10.5 bp的螺旋重复。游离DNA与蛋白质结合的DNA之间的比较表明，蛋白质直接接触的DNA区域的内在结构以及未被蛋白质接触的DNA区域的可变形性对于序列特异性蛋白质/DNA识别至关重要，因此对于病毒系统中的基因调控信号也至关重要。我们表明，当沿着DNA螺旋以正确的间隔定位时，选择具有适当构象特征的二核苷酸或更长片段可以构成调节蛋白识别DNA的结构密码。这种结构密码有助于形成互补的蛋白质-DNA界面，该界面可以通过蛋白质氨基酸与DNA碱基之间的氢键和非极性相互作用进一步确定。
