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Biomolecular condensates formed by designer minimalistic peptides

Author

Listed:
  • Avigail Baruch Leshem

    (Tel Aviv University)

  • Sian Sloan-Dennison

    (University of Strathclyde)

  • Tlalit Massarano

    (Tel Aviv University)

  • Shavit Ben-David

    (Tel Aviv University)

  • Duncan Graham

    (University of Strathclyde)

  • Karen Faulds

    (University of Strathclyde)

  • Hugo E. Gottlieb

    (Bar Ilan University)

  • Jordan H. Chill

    (Bar Ilan University)

  • Ayala Lampel

    (Tel Aviv University
    Center for Nanoscience and Nanotechnology Tel Aviv University
    Sagol Center for Regenerative Biotechnology Tel Aviv University
    Center for the Physics and Chemistry of Living Systems Tel Aviv University, Tel Aviv 69978, Israel)

Abstract

Inspired by the role of intracellular liquid-liquid phase separation (LLPS) in formation of membraneless organelles, there is great interest in developing dynamic compartments formed by LLPS of intrinsically disordered proteins (IDPs) or short peptides. However, the molecular mechanisms underlying the formation of biomolecular condensates have not been fully elucidated, rendering on-demand design of synthetic condensates with tailored physico-chemical functionalities a significant challenge. To address this need, here we design a library of LLPS-promoting peptide building blocks composed of various assembly domains. We show that the LLPS propensity, dynamics, and encapsulation efficiency of compartments can be tuned by changes to the peptide composition. Specifically, with the aid of Raman and NMR spectroscopy, we show that interactions between arginine and aromatic amino acids underlie droplet formation, and that both intra- and intermolecular interactions dictate droplet dynamics. The resulting sequence-structure-function correlation could support the future development of compartments for a variety of applications.

Suggested Citation

  • Avigail Baruch Leshem & Sian Sloan-Dennison & Tlalit Massarano & Shavit Ben-David & Duncan Graham & Karen Faulds & Hugo E. Gottlieb & Jordan H. Chill & Ayala Lampel, 2023. "Biomolecular condensates formed by designer minimalistic peptides," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36060-8
    DOI: 10.1038/s41467-023-36060-8
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    References listed on IDEAS

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    1. Bartosz Gabryelczyk & Hao Cai & Xiangyan Shi & Yue Sun & Piet J. M. Swinkels & Stefan Salentinig & Konstantin Pervushin & Ali Miserez, 2019. "Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    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.
    3. Carsten Donau & Fabian Späth & Marilyne Sosson & Brigitte A. K. Kriebisch & Fabian Schnitter & Marta Tena-Solsona & Hyun-Seo Kang & Elia Salibi & Michael Sattler & Hannes Mutschler & Job Boekhoven, 2020. "Active coacervate droplets as a model for membraneless organelles and protocells," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    4. Georg Krainer & Timothy J. Welsh & Jerelle A. Joseph & Jorge R. Espinosa & Sina Wittmann & Ella Csilléry & Akshay Sridhar & Zenon Toprakcioglu & Giedre Gudiškytė & Magdalena A. Czekalska & William E. , 2021. "Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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    Cited by:

    1. Shoupeng Cao & Tsvetomir Ivanov & Julian Heuer & Calum T. J. Ferguson & Katharina Landfester & Lucas Caire da Silva, 2024. "Dipeptide coacervates as artificial membraneless organelles for bioorthogonal catalysis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Maruša Ramšak & Dominique A. Ramirez & Loren E. Hough & Michael R. Shirts & Sara Vidmar & Kristina Eleršič Filipič & Gregor Anderluh & Roman Jerala, 2023. "Programmable de novo designed coiled coil-mediated phase separation in mammalian cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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