Intrinsically disordered proteins as crucial constituents of cellular aqueous two phase systems and coacervates

• Eukaryotic cells contain various membrane-less organelles.
• Such organelles can be generated due to the liquid–liquid phase separations.
• Membrane-less organelles represent cellular aqueous two phase systems (ATPSes).
• Intrinsically disordered proteins (IDPs) are crucial for generation of these organelles.

Here, we hypothesize that intrinsically disordered proteins (IDPs) serve as important drivers of the intracellular liquid–liquid phase separations that generate various membrane-less organelles. This hypothesis is supported by the overwhelming abundance of IDPs in these organelles. Assembly and disassembly of these organelles are controlled by changes in the concentrations of IDPs, their posttranslational modifications, binding of specific partners, and changes in the pH and/or temperature of the solution. Each resulting phase provides a distinct solvent environment for other solutes leading to their unequal distribution within phases. The specificity and efficiency of such partitioning is determined by the nature of the IDP(s) and defines “targeted” enrichment of specific molecules in the resulting membrane-less organelles that determines their specific activities.