De novo designed YK peptides forming reversible amyloid for synthetic protein condensates in mammalian cells - PubMed (original) (raw)

. 2024 Oct 18;15(1):8503.

doi: 10.1038/s41467-024-52708-5.

Affiliations

Free article

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

Takayuki Miki et al. Nat Commun. 2024.

Free article

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.

© 2024. The Author(s).

PubMed Disclaimer

References

    1. Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: Organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017). - PubMed - PMC - DOI
    1. Shin, Y. & Brangwynne, C. P. Liquid phase condensation in cell physiology and disease. Science 357, eaaf4382 (2017). - PubMed - DOI
    1. Hirose, T., Ninomiya, K., Nakagawa, S. & Yamazaki, T. A guide to membraneless organelles and their various roles in gene regulation. Nat. Rev. Mol. Cell Biol. 24, 288–304 (2023). - PubMed - DOI
    1. Banani, S. F. et al. Compositional Control of Phase-Separated Cellular Bodies. Cell 166, 651–663 (2016). - PubMed - PMC - DOI
    1. Yoshikawa, M., Yoshii, T., Ikuta, M. & Tsukiji, S. Synthetic Protein Condensates That Inducibly Recruit and Release Protein Activity in Living Cells. J. Am. Chem. Soc. 143, 6434–6446 (2021). - PubMed - DOI

MeSH terms

Substances

Grants and funding

LinkOut - more resources