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


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Article Info

DATE

2020-11-04

AUTHORS

W. Michael Babinchak, Benjamin K. Dumm, Sarah Venus, Solomiia Boyko, Andrea A. Putnam, Eckhard Jankowsky, Witold K. Surewicz

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. More... »

PAGES

5574

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-020-19211-z

    DOI

    http://dx.doi.org/10.1038/s41467-020-19211-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1132287391

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33149109


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