Segrosome structure revealed by a complex of ParR with centromere DNA
Segrosome structure revealed by a complex of ParR with centromere DNA
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DOI：
10.1038/nature06392
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发表时间：
2007-12-20
期刊：
影响因子：
64.8
通讯作者：
Firth, Neville
中科院分区：
文献类型：
--
作者：
Schumacher, Maria A.;Glover, Tiffany C.;Firth, Neville
遗传物质的稳定遗传依赖于精确的DNA分割。质粒作为易于处理的模型系统来研究DNA分离，因为它们只需要一个DNA着丝粒、一个着丝粒结合蛋白和一个产生力的三磷酸腺苷酶。分割（par）系统的着丝粒通常由直接重复序列的串联排列组成（1-7）。最典型的par系统包含着丝粒结合蛋白ParR和atp酶ParM。在分离的第一步，多个ParR蛋白与着丝粒重复序列相互作用，形成一个结构未知的大型核蛋白复合物，称为segrosome，它结合ParM细丝（4,8-10）。pSK41 ParR结合由多个20碱基对（bp）串联重复序列组成的着丝粒，介导转录自调节和分离。在这里，我们报道了pSK41 segrosome在ParR - DNA复合体的晶体结构中揭示的结构。在晶体中，20聚串联重复序列伪连续叠加产生全长着丝粒，ParR的带状-螺旋-螺旋（RHH）折叠结合连续DNA重复序列作为二聚体的二聚体。值得注意的是，二聚体的二聚体组装成一个连续的蛋白质超螺旋阵列，将DNA包裹在其正凸表面，形成一个开放的螺线形结构的大segrosome，这表明ParM捕获和随后的质粒分离的机制。
The stable inheritance of genetic material depends on accurate DNA partition. Plasmids serve as tractable model systems to study DNA segregation because they require only a DNA centromere, a centromere- binding protein and a force- generating ATPase. The centromeres of partition ( par) systems typically consist of a tandem arrangement of direct repeats(1-7). The best- characterized par system contains a centromere- binding protein called ParR and an ATPase called ParM. In the first step of segregation, multiple ParR proteins interact with the centromere repeats to form a large nucleoprotein complex of unknown structure called the segrosome, which binds ParM filaments(4,8-10). pSK41 ParR binds a centromere consisting of multiple 20- base- pair ( bp) tandem repeats to mediate both transcription autoregulation and segregation. Here we report the structure of the pSK41 segrosome revealed in the crystal structure of a ParR - DNA complex. In the crystals, the 20- mer tandem repeats stack pseudo- continuously to generate the full- length centromere with the ribbon - helix - helix ( RHH) fold of ParR binding successive DNA repeats as dimer- of- dimers. Remarkably, the dimer- of- dimers assemble in a continuous protein super- helical array, wrapping the DNA about its positive convex surface to form a large segrosome with an open, solenoid-shaped structure, suggesting a mechanism for ParM capture and subsequent plasmid segregation.