Stochastic Self-Assembly of ParB Proteins Builds the Bacterial DNA Segregation Apparatus
Stochastic Self-Assembly of ParB Proteins Builds the Bacterial DNA Segregation Apparatus
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DOI：
10.1016/j.cels.2015.07.013
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发表时间：
2015-08-26
期刊：
影响因子：
9.3
通讯作者：
Bouet, Jean-Yves
中科院分区：
文献类型：
--
作者：
Sanchez, Aurore;Cattoni, Diego I.;Bouet, Jean-Yves
分子生物学中的许多典型过程依赖于高阶核蛋白复合物的动态组装。在细菌中，ParABS的组装机制，核蛋白超复合物，积极分离细菌染色体和许多质粒，仍然难以捉摸。我们结合了超分辨率显微镜，定量全基因组调查，生物化学和数学建模，以调查组装的ParB在着丝粒样序列parS。我们发现几乎所有ParB分子都通过蛋白质-蛋白质和蛋白质-DNA相互作用的协同网络主动限制在parS周围。通过建模对经验确定的高分辨率ParB基因组分布进行询问表明，ParB不是仅与特定序列结合并随后扩散，而是在parS周围长距离结合随机蛋白。我们提出了一个新的模型形成的ParABS分区复合物的成核和笼：ParB形成一个动态的晶格与周围的DNA parS。这种组装模型和方法来表征大规模的，动态的大分子之间的相互作用，可以推广到许多不相关的机器，自组装在上层建筑。
Many canonical processes in molecular biology rely on the dynamic assembly of higher-order nucleoprotein complexes. In bacteria, the assembly mechanism of ParABS, the nucleoprotein super-complex that actively segregates the bacterial chromosome and many plasmids, remains elusive. We combined super-resolution microscopy, quantitative genomewide surveys, biochemistry, and mathematical modeling to investigate the assembly of ParB at the centromere-like sequences parS. We found that nearly all ParB molecules are actively confined around parS by a network of synergistic protein-protein and protein-DNA interactions. Interrogation of the empirically determined, high-resolution ParB genomic distribution with modeling suggests that instead of binding only to specific sequences and subsequently spreading, ParB binds stochastically around parS over long distances. We propose a new model for the formation of the ParABS partition complex based on nucleation and caging: ParB forms a dynamic lattice with the DNA around parS. This assembly model and approach to characterizing large-scale, dynamic interactions between macromolecules may be generalizable to many unrelated machineries that self-assemble in superstructures.