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Abstract：
Biomolecular condensates (BMCs) exhibit physiological and pathological relevance in biological systems. Both liquid and solid condensates play significant roles in the spatiotemporal regulation and organization of macromolecules and their biological activities. Some pathological solid condensates, such as Lewy Bodies and other fibrillar aggregates, have been hypothesized to originate from liquid condensates. With the prevalence of BMCs having functional and dysfunctional roles, it is imperative to understand the mechanism of biomolecular condensate formation and initiation. Using the low-complexity domain (LCD) of heterogenous ribonuclear protein A1 (hnRNPA1) as our model, we monitored initial assembly events using dynamic light scattering (DLS) while modulating pH and salt conditions to perturb macromolecule and condensate properties. We observed the formation of nanometer-sized BMCs (nano-condensates) distinct from protein monomers and micron-sized condensates. We also observed that conditions that solubilize micron-sized protein condensates do not solubilize nano-condensates, indicating that the balance of forces that stabilize nano-condensates and micron-sized condensates are distinct. These findings provide insight into the forces that drive protein phase separation and potential nucleation structures of macromolecular condensation.
摘要：
生物分子缩合物(BMC)在生物系统中表现出生理和病理相关性。液体和固体凝聚体在大分子的时空调控和组织及其生物活性中起着重要作用。一些病理性固体冷凝物，如路易体和其他纤维状聚集体，已经被假设来自液体冷凝物。随着BMC具有功能和功能失调作用的患病率，了解生物分子缩合物形成和引发的机理势在必行。使用异质核糖核蛋白A1（hnRNPA1）的低复杂度域（LCD）作为我们的模型，我们使用动态光散射（DLS）监测初始组装事件，同时调节pH和盐条件以干扰大分子和缩合物特性。我们观察到与蛋白质单体和微米大小的缩合物不同的纳米大小的BMC(纳米缩合物)的形成。我们还观察到，溶解微米大小的蛋白质缩合物的条件不溶解纳米缩合物，表明稳定纳米冷凝物和微米级冷凝物的力的平衡是不同的。这些发现提供了对驱动蛋白质相分离和大分子缩合的潜在成核结构的力的洞察。
