Widespread occurrence of the droplet state of proteins in the human proteome

Maarten Hardenberg, Attila Horvath, Viktor Ambrus, Monika Fuxreiter*, Michele Vendruscolo*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    197 Citations (Scopus)

    Abstract

    A wide range of proteins have been reported to condensate into a dense liquid phase, forming a reversible droplet state. Failure in the control of the droplet state can lead to the formation of the more stable amyloid state, which is often disease-related. These observations prompt the question of how many proteins can undergo liquid–liquid phase separation. Here, in order to address this problem, we discuss the biophysical principles underlying the droplet state of proteins by analyzing current evidence for droplet-driver and droplet-client proteins. Based on the concept that the droplet state is stabilized by the large conformational entropy associated with nonspecific side-chain interactions, we develop the FuzDrop method to predict droplet-promoting regions and proteins, which can spontaneously phase separate. We use this approach to carry out a proteome-level study to rank proteins according to their propensity to form the droplet state, spontaneously or via partner interactions. Our results lead to the conclusion that the droplet state could be, at least transiently, accessible to most proteins under conditions found in the cellular environment.

    Original languageEnglish
    Pages (from-to)33254-33262
    Number of pages9
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume117
    Issue number52
    DOIs
    Publication statusPublished - Dec 2020

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