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Hydrophobicity of arginine leads to reentrant liquid-liquid phase separation behaviors of arginine-rich proteins

Author

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  • Yuri Hong

    (Pohang University of Science and Technology (POSTECH)
    Pohang University of Science and Technology (POSTECH))

  • Saeed Najafi

    (University of California)

  • Thomas Casey

    (University of California)

  • Joan-Emma Shea

    (University of California)

  • Song-I Han

    (University of California
    University of California)

  • Dong Soo Hwang

    (Pohang University of Science and Technology (POSTECH)
    Pohang University of Science and Technology (POSTECH))

Abstract

Intrinsically disordered proteins rich in cationic amino acid groups can undergo Liquid-Liquid Phase Separation (LLPS) in the presence of charge-balancing anionic counterparts. Arginine and Lysine are the two most prevalent cationic amino acids in proteins that undergo LLPS, with arginine-rich proteins observed to undergo LLPS more readily than lysine-rich proteins, a feature commonly attributed to arginine’s ability to form stronger cation-π interactions with aromatic groups. Here, we show that arginine’s ability to promote LLPS is independent of the presence of aromatic partners, and that arginine-rich peptides, but not lysine-rich peptides, display re-entrant phase behavior at high salt concentrations. We further demonstrate that the hydrophobicity of arginine is the determining factor giving rise to the reentrant phase behavior and tunable viscoelastic properties of the dense LLPS phase. Controlling arginine-induced reentrant LLPS behavior using temperature and salt concentration opens avenues for the bioengineering of stress-triggered biological phenomena and drug delivery systems.

Suggested Citation

  • Yuri Hong & Saeed Najafi & Thomas Casey & Joan-Emma Shea & Song-I Han & Dong Soo Hwang, 2022. "Hydrophobicity of arginine leads to reentrant liquid-liquid phase separation behaviors of arginine-rich proteins," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35001-1
    DOI: 10.1038/s41467-022-35001-1
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    References listed on IDEAS

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    2. Rachel S. Fisher & Shana Elbaum-Garfinkle, 2020. "Tunable multiphase dynamics of arginine and lysine liquid condensates," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
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