Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending
Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending
复制标题
DOI：
10.7554/elife.19706
复制
发表时间：
2016-12-23
期刊：
影响因子：
7.7
通讯作者：
Barabas, Orsolya
中科院分区：
文献类型：
--
作者：
Bebel, Aleksandra;Karaca, Ezgi;Barabas, Orsolya
细菌Xer位点特异性重组酶通过解联染色体多聚体发挥重要的基因组维持作用，但其作用机制在结构上尚未明确。在这里，我们展示了两个高分辨率结构的幽门螺杆菌XerH及其重组位点DNA dif(H)，代表了重组途径中的裂解前和裂解后突触中间体。这些结构揭示了DNA链切割和重新连接的激活涉及到大的构象变化和DNA弯曲，这表明与细胞分裂蛋白FtsK的相互作用可能导致隔膜的重组。结合生物化学和体内分析，我们的结构还揭示了dif(H)的小序列不对称如何定义突触复合体中的蛋白质构象并协调DNA链交换的顺序。我们的研究结果揭示了Xer重组的催化机制和细胞分裂过程中重组活性的调控模型。
Bacterial Xer site-specific recombinases play an essential genome maintenance role by unlinking chromosome multimers, but their mechanism of action has remained structurally uncharacterized. Here, we present two high-resolution structures of Helicobacter pylori XerH with its recombination site DNA dif(H), representing pre-cleavage and post-cleavage synaptic intermediates in the recombination pathway. The structures reveal that activation of DNA strand cleavage and rejoining involves large conformational changes and DNA bending, suggesting how interaction with the cell division protein FtsK may license recombination at the septum. Together with biochemical and in vivo analysis, our structures also reveal how a small sequence asymmetry in dif(H) defines protein conformation in the synaptic complex and orchestrates the order of DNA strand exchanges. Our results provide insights into the catalytic mechanism of Xer recombination and a model for regulation of recombination activity during cell division.