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

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  • Hao-Yu Chuang

    (Academia Sinica
    Academia Sinica
    National Tsing Hua University)

  • Ruei-Yu He

    (Academia Sinica)

  • Yung-An Huang

    (Academia Sinica)

  • Wan-Ting Hsu

    (Academia Sinica)

  • Ya-Jen Cheng

    (Academia Sinica
    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
    Academia Sinica
    Academia Sinica
    National Chiayi University)

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.

Suggested Citation

  • 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, 2024. "Engineered droplet-forming peptide as photocontrollable phase modulator for fused in sarcoma protein," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50025-5
    DOI: 10.1038/s41467-024-50025-5
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    References listed on IDEAS

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    1. Benjamin S. Schuster & Ellen H. Reed & Ranganath Parthasarathy & Craig N. Jahnke & Reese M. Caldwell & Jessica G. Bermudez & Holly Ramage & Matthew C. Good & Daniel A. Hammer, 2018. "Controllable protein phase separation and modular recruitment to form responsive membraneless organelles," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. W. Michael Babinchak & Benjamin K. Dumm & Sarah Venus & Solomiia Boyko & Andrea A. Putnam & Eckhard Jankowsky & Witold K. Surewicz, 2020. "Small molecules as potent biphasic modulators of protein liquid-liquid phase separation," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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