IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-19211-z.html
   My bibliography  Save this article

Small molecules as potent biphasic modulators of protein liquid-liquid phase separation

Author

Listed:
  • W. Michael Babinchak

    (Case Western Reserve University)

  • Benjamin K. Dumm

    (Case Western Reserve University)

  • Sarah Venus

    (Case Western Reserve University)

  • Solomiia Boyko

    (Case Western Reserve University)

  • Andrea A. Putnam

    (Case Western Reserve University
    Johns Hopkins School of Medicine)

  • Eckhard Jankowsky

    (Case Western Reserve University)

  • Witold K. Surewicz

    (Case Western Reserve University)

Abstract

Liquid-liquid phase separation (LLPS) of proteins that leads to formation of membrane-less organelles is critical to many biochemical processes in the cell. However, dysregulated LLPS can also facilitate aberrant phase transitions and lead to protein aggregation and disease. Accordingly, there is great interest in identifying small molecules that modulate LLPS. Here, we demonstrate that 4,4’-dianilino-1,1’-binaphthyl-5,5’-disulfonic acid (bis-ANS) and similar compounds are potent biphasic modulators of protein LLPS. Depending on context, bis-ANS can both induce LLPS de novo as well as prevent formation of homotypic liquid droplets. Our study also reveals the mechanisms by which bis-ANS and related compounds modulate LLPS and identify key chemical features of small molecules required for this activity. These findings may provide a foundation for the rational design of small molecule modulators of LLPS with therapeutic value.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19211-z
    DOI: 10.1038/s41467-020-19211-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-19211-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-19211-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. William E. Arter & Runzhang Qi & Nadia A. Erkamp & Georg Krainer & Kieran Didi & Timothy J. Welsh & Julia Acker & Jonathan Nixon-Abell & Seema Qamar & Jordina Guillén-Boixet & Titus M. Franzmann & Dav, 2022. "Biomolecular condensate phase diagrams with a combinatorial microdroplet platform," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Chenyang Lan & Juhyeong Kim & Svenja Ulferts & Fernando Aprile-Garcia & Sophie Weyrauch & Abhinaya Anandamurugan & Robert Grosse & Ritwick Sawarkar & Aleks Reinhardt & Thorsten Hugel, 2023. "Quantitative real-time in-cell imaging reveals heterogeneous clusters of proteins prior to condensation," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    3. Jun Sun & Jiale Qu & Cai Zhao & Xinyao Zhang & Xinyu Liu & Jia Wang & Chao Wei & Xinyi Liu & Mulan Wang & Pengguihang Zeng & Xiuxiao Tang & Xiaoru Ling & Li Qing & Shaoshuai Jiang & Jiahao Chen & Tara, 2024. "Precise prediction of phase-separation key residues by machine learning," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Hong Zhang & Huazhang Guo & Danni Li & Yiling Zhang & Shengnan Zhang & Wenyan Kang & Cong Liu & Weidong Le & Liang Wang & Dan Li & Bin Dai, 2024. "Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. 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.
    6. Xi Li & Linwei Yu & Xikai Liu & Tianyi Shi & Yu Zhang & Yushuo Xiao & Chen Wang & Liangliang Song & Ning Li & Xinran Liu & Yuchen Chen & Robert B. Petersen & Xiang Cheng & Weikang Xue & Yanxun V. Yu &, 2024. "β-synuclein regulates the phase transitions and amyloid conversion of α-synuclein," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19211-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.