研究动态
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工程化的液滴形成肽作为光控相位调制器,用于融合在肉瘤蛋白中。

Engineered droplet-forming peptide as photocontrollable phase modulator for fused in sarcoma protein.

发表日期:2024 Jul 06
作者: Hao-Yu Chuang, Ruei-Yu He, Yung-An Huang, Wan-Ting Hsu, Ya-Jen Cheng, Zheng-Rong Guo, Niaz Wali, Ing-Shouh Hwang, Jiun-Jie Shie, Joseph Jen-Tse Huang
来源: MOLECULAR & CELLULAR PROTEOMICS

摘要:

生物分子凝聚体的组装和分解对于控制细胞反应中生物分子的亚细胞区划至关重要。最近,人们发现疾病中冷凝物的相变与其成熟(聚集)过程之间存在相关性。因此,调节冷凝物的相以揭示冷凝的作用已成为人们感兴趣的问题。在这里,我们创建了一种基于肽的相位调制器 JSF1,它在黑暗中形成液滴,并在光引发时转化为类淀粉样原纤维,其独特的纳米力学和动态特性证明了这一点。研究发现,JSF1 可有效增强纯化的肉瘤融合蛋白 (FUS) 的浓缩,并在光照下诱导其纤维化。我们还使用 JSF1 调节活细胞中 FUS 凝聚物的生物物理状态,并阐明 FUS 相变和 FUS 蛋白病之间的关系,从而揭示蛋白质相变对细胞功能和故障的影响。© 2024。 )。
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.© 2024. The Author(s).