The Role of Post-Translational Modifications in the Phase Transitions of Intrinsically Disordered Proteins - PubMed (original) (raw)

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The Role of Post-Translational Modifications in the Phase Transitions of Intrinsically Disordered Proteins

Izzy Owen et al. Int J Mol Sci. 2019.

Abstract

Advances in genomics and proteomics have revealed eukaryotic proteomes to be highly abundant in intrinsically disordered proteins that are susceptible to diverse post-translational modifications. Intrinsically disordered regions are critical to the liquid-liquid phase separation that facilitates specialized cellular functions. Here, we discuss how post-translational modifications of intrinsically disordered protein segments can regulate the molecular condensation of macromolecules into functional phase-separated complexes.

Keywords: intrinsically disordered regions; liquid–liquid phase separation; membraneless organelles; post-translational modifications.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1

Figure 1

Liquid–liquid phase separation (LLPS) of biopolymers, such as proteins and RNA, is a mechanism by which cells organize their contents into specific functional structures called membraneless organelles (MLOs). Post-translational modifications (PTMs) of intrinsically disordered proteins can influence LLPS and thus regulate the formation and dissolution of MLOs. The figure depicts different patterns of PTMs favoring dispersed or condensed states. Changes in the material properties of liquid-phase separated granules are hypothesized to cause some neurodegenerative diseases. According to this hypothesis, droplets lose their liquid (reversible) properties and adopt more rigid (less reversible) internal structures, which may be glass-like, or in some cases, may have solid amyloid-like structures. These irreversible phase states may have gain-of-function toxicity to neurons.

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