Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter
Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter
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DOI：
10.1038/nsmb.2160
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发表时间：
2011-11-01
影响因子：
16.8
通讯作者：
Sola, Maria
中科院分区：
文献类型：
--
作者：
Rubio-Cosials, Anna;Sidow, Jasmin F.;Sola, Maria
人线粒体转录因子A（TFAM）是线粒体DNA包装和维持所必需的，并且在转录中也具有关键作用。晶体学分析的TFAM在复合物中含有线粒体轻链启动子（LSP）的寡核苷酸揭示了两个高迁移率族（HMG）蛋白质结构域，通过不同的DNA识别特性，嵌入在两个反向的DNA基序的残基。这诱导了类似于180度的总体DNA弯曲，通过结构域间接头稳定。这种U形转弯允许TFAM C末端尾（其募集转录机器）接近起始位点，尽管接触了远处的DNA序列。我们还确定，在没有DNA的情况下，晶体中与DNA接触的结构化蛋白质区域在溶液中是高度灵活的。我们的数据表明，TFAM弯曲LSP创建一个最佳的DNA排列的转录起始，同时促进DNA压缩在基因组的其他地方。
Human mitochondrial transcription factor A, TFAM, is essential for mitochondrial DNA packaging and maintenance and also has a crucial role in transcription. Crystallographic analysis of TFAM in complex with an oligonucleotide containing the mitochondrial light strand promoter (LSP) revealed two high-mobility group (HMG) protein domains that, through different DNA recognition properties, intercalate residues at two inverted DNA motifs. This induced an overall DNA bend of similar to 180 degrees, stabilized by the interdomain linker. This U-turn allows the TFAM C-terminal tail, which recruits the transcription machinery, to approach the initiation site, despite contacting a distant DNA sequence. We also ascertained that structured protein regions contacting DNA in the crystal were highly flexible in solution in the absence of DNA. Our data suggest that TFAM bends LSP to create an optimal DNA arrangement for transcriptional initiation while facilitating DNA compaction elsewhere in the genome.