Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan.
Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan.
Nat Commun. 2024 Jul 6;15(1):5686. doi: 10.1038/s41467-024-50025-5.
The assembly and disassembly of biomolecular condensates are crucial for the subcellular compartmentalization of biomolecules in the control of cellular reactions. Recently, a correlation has been discovered between the phase transition of condensates and their maturation (aggregation) process in diseases. Therefore, modulating the phase of condensates to unravel the roles of condensation has become a matter of interest. Here, we create a peptide-based phase modulator, JSF1, which forms droplets in the dark and transforms into amyloid-like fibrils upon photoinitiation, as evidenced by their distinctive nanomechanical and dynamic properties. JSF1 is found to effectively enhance the condensation of purified fused in sarcoma (FUS) protein and, upon light exposure, induce its fibrilization. We also use JSF1 to modulate the biophysical states of FUS condensates in live cells and elucidate the relationship between FUS phase transition and FUS proteinopathy, thereby shedding light on the effect of protein phase transition on cellular function and malfunction.
生物分子凝聚体的组装和拆卸对于控制细胞反应中生物分子的亚细胞区室化至关重要。最近，人们发现凝聚体的相变与其在疾病中的成熟（聚集）过程之间存在相关性。因此，调节凝聚体的相以揭示凝聚的作用成为了一个研究热点。在这里，我们创建了一种基于肽的相调节剂 JSF1，它在黑暗中形成液滴，在光引发下转化为类似淀粉样的原纤维，这可以从其独特的纳米力学和动态特性中得到证明。JSF1 被发现可以有效地增强纯化的肉瘤中融合（FUS）蛋白的凝聚，并在光照下诱导其纤维化。我们还使用 JSF1 来调节活细胞中 FUS 凝聚体的生物物理状态，并阐明 FUS 相变与 FUS 蛋白病之间的关系，从而揭示了蛋白质相变对细胞功能和故障的影响。
