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

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 and Joseph Jen-Tse Huang ()
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Hao-Yu Chuang: Academia Sinica
Ruei-Yu He: Academia Sinica
Yung-An Huang: Academia Sinica
Wan-Ting Hsu: Academia Sinica
Ya-Jen Cheng: Academia Sinica
Zheng-Rong Guo: Academia Sinica
Niaz Wali: Academia Sinica
Ing-Shouh Hwang: Academia Sinica
Jiun-Jie Shie: Academia Sinica
Joseph Jen-Tse Huang: Academia Sinica

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-50025-5

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