Protein intrinsic disorder-based liquid-liquid phase transitions in biological systems: Complex coacervates and membrane-less organelles

•Eukaryotic cells contain numerous membrane-less organelles with different compositions.•These organelles are formed in response to changes in the cellular environment.•They are products of the reversible and highly controlled liquid-liquid phase transitions.•Major proteinaceous constituents of these organelles are intrinsically disordered proteins.•Lack of stable structure in these proteins is crucial for the formation of phase-separated droplets.

It is clear now that eukaryotic cells contain numerous membrane-less organelles, many of which are formed in response to changes in the cellular environment. Being typically liquid in nature, many of these organelles can be described as products of the reversible and highly controlled liquid-liquid phase transitions in biological systems. Many of these membrane-less organelles are complex coacervates containing (almost invariantly) intrinsically disordered proteins and often nucleic acids. It seems that the lack of stable structure in major proteinaceous constituents of these organelles is crucial for the formation of phase-separated droplets. This review considers several biologically relevant liquid-liquid phase transitions, introduces some general features attributed to intrinsically disordered proteins, represents several illustrative examples of intrinsic disorder-based phase separation, and provides some reasons for the abundance of intrinsically disordered proteins in organelles formed as a result of biological liquid-liquid phase transitions.

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