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

Autor: Chuang HY; Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan.; Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan.; Department of Chemistry, National Tsing Hua University, Hsinchu, 300, Taiwan., He RY; Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan., Huang YA; Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan., Hsu WT; Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan., Cheng YJ; Neuroscience Program of Academia Sinica, Academia Sinica, Taipei, 115, Taiwan.; Institute of Molecular Biology, Academia Sinica, Taipei, 115, Taiwan., Guo ZR; Institute of Physics, Academia Sinica, Taipei, 115, Taiwan., Wali N; Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan., Hwang IS; Institute of Physics, Academia Sinica, Taipei, 115, Taiwan., Shie JJ; Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan., Huang JJ; Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan. jthuang@gate.sinica.edu.tw.; Neuroscience Program of Academia Sinica, Academia Sinica, Taipei, 115, Taiwan. jthuang@gate.sinica.edu.tw.; Sustainable Chemical Science and Technology, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan. jthuang@gate.sinica.edu.tw.; Department of Applied Chemistry, National Chiayi University, Chiayi City, 600, Taiwan. jthuang@gate.sinica.edu.tw.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 06; Vol. 15 (1), pp. 5686. Date of Electronic Publication: 2024 Jul 06.
DOI: 10.1038/s41467-024-50025-5
Abstrakt: 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).)
Databáze: MEDLINE
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