Ion binding with charge inversion combined with screening modulates DEAD box helicase phase transitions.
Ion binding with charge inversion combined with screening modulates DEAD box helicase phase transitions.
复制标题
离子结合与电荷反转结合筛选调节 DEAD 盒解旋酶相变。
DOI：
10.1016/j.celrep.2023.113375
复制
发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Crabtree MD
中科院分区：
文献类型：
--
作者：
Crabtree MD
无膜细胞器或生物分子凝聚物使细胞能够将物质和过程划分为独特的生物化学环境。虽然已知特定的吸引性分子相互作用可以稳定生物分子凝聚物，但排斥性相互作用以及这些相反力之间的平衡在很大程度上尚未探索。在这里，我们表明，排斥和吸引静电相互作用调节冷凝物的稳定性，内部流动性，接口，和选择性分区的分子bothin体外和细胞。我们发现，信号离子，如钙，改变模型Ddx 3和Ddx 4缩合物蛋白之间的排斥直接结合到带负电荷的氨基酸侧链，并有效地反转其电荷，在一个根本上不同的方式静电屏蔽。使用聚合模型结合广义贴纸和间隔，我们准确地量化和预测冷凝物的稳定性在很宽的pH值，盐浓度和氨基酸序列。我们的模型提供了一个通用的定量处理了解电荷和离子如何可逆地控制冷凝物的稳定性。
Membraneless organelles, or biomolecular condensates, enable cells to compartmentalize material and processes into unique biochemical environments. While specific, attractive molecular interactions are known to stabilize biomolecular condensates, repulsive interactions, and the balance between these opposing forces, are largely unexplored. Here, we demonstrate that repulsive and attractive electrostatic interactions regulate condensate stability, internal mobility, interfaces, and selective partitioning of molecules bothin vitroand in cells. We find that signaling ions, such as calcium, alter repulsions between model Ddx3 and Ddx4 condensate proteins by directly binding to negatively charged amino acid sidechains and effectively inverting their charge, in a manner fundamentally dissimilar to electrostatic screening. Using a polymerization model combined with generalized stickers and spacers, we accurately quantify and predict condensate stability over a wide range of pH, salt concentrations, and amino acid sequences. Our model provides a general quantitative treatment for understanding how charge and ions reversibly control condensate stability.