Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan.
Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
Nucleic Acids Res. 2021 Dec 16;49(22):13150-13164. doi: 10.1093/nar/gkab1155.
Genome segregation is a vital process in all organisms. Chromosome partitioning remains obscure in Archaea, the third domain of life. Here, we investigated the SegAB system from Sulfolobus solfataricus. SegA is a ParA Walker-type ATPase and SegB is a site-specific DNA-binding protein. We determined the structures of both proteins and those of SegA-DNA and SegB-DNA complexes. The SegA structure revealed an atypical, novel non-sandwich dimer that binds DNA either in the presence or in the absence of ATP. The SegB structure disclosed a ribbon-helix-helix motif through which the protein binds DNA site specifically. The association of multiple interacting SegB dimers with the DNA results in a higher order chromatin-like structure. The unstructured SegB N-terminus plays an essential catalytic role in stimulating SegA ATPase activity and an architectural regulatory role in segrosome (SegA-SegB-DNA) formation. Electron microscopy results also provide a compact ring-like segrosome structure related to chromosome organization. These findings contribute a novel mechanistic perspective on archaeal chromosome segregation.
基因组分离是所有生物的一个重要过程。在古菌(生命的第三个域)中,染色体的分配仍然不清楚。在这里,我们研究了来自嗜热硫化叶菌的 SegAB 系统。SegA 是一种 ParA Walker 型 ATP 酶,SegB 是一种特定于位点的 DNA 结合蛋白。我们确定了这两种蛋白质以及 SegA-DNA 和 SegB-DNA 复合物的结构。SegA 结构揭示了一种非典型的新型非夹层二聚体,它可以在有或没有 ATP 的情况下结合 DNA。SegB 结构揭示了一种通过该结构蛋白特异性结合 DNA 的 ribbon-helix-helix 基序。多个相互作用的 SegB 二聚体与 DNA 的结合导致更高阶的染色质样结构。未结构化的 SegB N 端在刺激 SegA ATP 酶活性方面发挥着重要的催化作用,并在 segrosome(SegA-SegB-DNA)形成中发挥结构调节作用。电子显微镜结果还提供了与染色体组织相关的紧凑环形 segrosome 结构。这些发现为古菌染色体分离提供了一种新颖的机制视角。