The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems.

The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems.
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天然和合成系统中细菌衍生的生物分子冷凝物调谐生物学功能的材料特性。

DOI:
10.1038/s41467-022-33221-z
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发表时间:
2022-09-26
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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细胞内相分离作为在时间和空间上组织生化反应的普遍原理而出现。生物功能如何在这些组件中编码以及这是否取决于它们的物质状态仍然没有完全解决。保守的内在无序蛋白PopZ在细菌新月柄杆菌的两极形成缩合物,这反过来又协调细胞周期调节信号级联。在这里,我们表明,这些凝聚物的材料性能是由螺旋低聚结构域和扩展的无序区域介导的吸引力和排斥力之间的平衡,分别确定。一系列PopZ突变体破坏了这种平衡,导致凝聚物跨越了从液体到固体的材料性质谱。一个狭窄的范围内的冷凝物材料的属性支持适当的细胞分裂,连接新兴的属性,以有机体的健身。我们利用这些见解将PopZ重新定位为一个模块化平台,用于在人类细胞中生成可调合成缩合物。“细胞内相分离正在成为在时间和空间上组织生化反应的普遍原则。在这里,作者展示了PopZ凝聚动力学支持细胞分裂,并使用PopZ模块化架构,开发了可调的PopTag平台,以实现设计师凝聚。
Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. It remains incompletely resolved how biological function is encoded in these assemblies and whether this depends on their material state. The conserved intrinsically disordered protein PopZ forms condensates at the poles of the bacterium Caulobacter crescentus, which in turn orchestrate cell-cycle regulating signaling cascades. Here we show that the material properties of these condensates are determined by a balance between attractive and repulsive forces mediated by a helical oligomerization domain and an expanded disordered region, respectively. A series of PopZ mutants disrupting this balance results in condensates that span the material properties spectrum, from liquid to solid. A narrow range of condensate material properties supports proper cell division, linking emergent properties to organismal fitness. We use these insights to repurpose PopZ as a modular platform for generating tunable synthetic condensates in human cells. “Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. Here the authors show that PopZ condensate dynamics support cell division and using PopZ modular architecture, the tunable PopTag platform was developed to enable designer condensates.”
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