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Segrosome structure revealed by a complex of ParR with centromere DNA

机译:ParR与着丝粒DNA的复合物揭示的脂质体结构

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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. 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 nudeoprotein complex of unknown structure called the segrosome, which binds ParM filaments. 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.
机译:遗传物质的稳定遗传取决于准确的DNA分配。质粒用作研究DNA分离的易于处理的模型系统,因为它们仅需要DNA着丝粒,着丝粒结合蛋白和产生力的ATPase。分区(par)系统的着丝粒通常由直接重复的串联排列组成。表征最好的par系统包含一个称为ParR的着丝粒结合蛋白和一个称为ParM的ATPase。在分离的第一步中,多个ParR蛋白与着丝粒重复序列相互作用,形成了一个未知结构的大裸蛋白复合物,称为segrosome,与ParM细丝结合。 pSK41 ParR结合由多个20个碱基对(bp)的串联重复序列组成的着丝粒,以介导转录自动调节和分离。在这里,我们报道了在ParR-DNA复合物的晶体结构中揭示的pSK41脂质体的结构。在晶体中,20-mer串联重复序列伪连续堆叠以产生全长着丝粒,结合ParR的带-螺旋-螺旋(RHH)折叠,连续的DNA重复为二聚体。值得注意的是,二聚体以连续的蛋白质超螺旋形阵列组装,将DNA包裹在其正凸表面周围,形成具有开放螺线管形结构的大脂质体,提示了ParM捕获和随后质粒分离的机制。

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