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.
Highlights
Introduction to LiquidLiquid Phase Separation and Membraneless OrganellesCells contain crowded molecular environments hosting discrete functions that must be separated within time and space
We evaluate the hypothesis that the combination of intrinsically disordered regions (IDRs) multivalency and the capacity to be extensively modified results in reversible networks of interactions that can be regulated by specific cellular cues (Figure 1)
Phosphoprotein is phosphorylated at multiple sites, but Serine 86 and Serine 151—both of which are in IDRs—have been identified as regulatory sites for inclusion bodies (IBs) formation
Summary
Cells contain crowded molecular environments hosting discrete functions that must be separated within time and space. Membrane-less compartments resulting from liquid–liquid phase separation (LLPS) are increasingly being recognized as mechanisms for organizing cellular activities These distinct regions may be referred to as biomolecular condensates or membrane-less organelles (MLOs). MLOs contain proteins, and frequently nucleic acids, and are dynamic in size (generally submicrometer), formation, and composition [1] They behave like liquid droplets, capable of fusing, deforming, and rearranging [2]—all while being solvated in the larger aqueous environment of the cell. Many proteins linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) can undergo LLPS and accumulate within MLOs [18] Mutations in these proteins cause disease but can alter LLPS and the physical properties of the phase-separated state [19,20]. It is hypothesized that aberrant irreversible phase transitions may result in proteinaceous neuronal inclusions that lead directly to cellular dysfunction [2]
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