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De novo designed YK peptides forming reversible amyloid for synthetic protein condensates in mammalian cells

Author

Listed:
  • Takayuki Miki

    (Tokyo Institute of Technology
    The University of Tokyo)

  • Masahiro Hashimoto

    (Tokyo Institute of Technology)

  • Hiroki Takahashi

    (Tokyo Institute of Technology)

  • Masatoshi Shimizu

    (Tokyo Institute of Technology
    The University of Tokyo)

  • Sae Nakayama

    (Tokyo Institute of Technology)

  • Tadaomi Furuta

    (Tokyo Institute of Technology)

  • Hisakazu Mihara

    (Tokyo Institute of Technology)

Abstract

In mammalian cells, protein condensates underlie diverse cell functions. Intensive synthetic biological research has been devoted to fabricating liquid droplets using de novo peptides/proteins designed from scratch in test tubes or bacterial cells. However, the development of de novo sequences for synthetic droplets forming in eukaryotes is challenging. Here, we report YK peptides, comprising 9–15 residues of alternating repeats of tyrosine and lysine, which form reversible amyloid-like fibrils accompanied by binding with poly-anion species such as ATP. By genetically tagging the YK peptide, superfolder GFPs assemble into artificial liquid-like droplets in living cells. Rational design of the YK system allows fine-tuning of the fluidity and construction of multi-component droplets. The YK system not only facilitates intracellular reconstitution of simplified models for natural protein condensates, but it also provides a toolbox for the systematic creation of droplets with different dynamics and composition for in situ evaluation.

Suggested Citation

  • Takayuki Miki & Masahiro Hashimoto & Hiroki Takahashi & Masatoshi Shimizu & Sae Nakayama & Tadaomi Furuta & Hisakazu Mihara, 2024. "De novo designed YK peptides forming reversible amyloid for synthetic protein condensates in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52708-5
    DOI: 10.1038/s41467-024-52708-5
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