Chapter 3 - Biochemical and structural biology aspects of liquid–liquid phase separation: protein side of liquid–liquid phase separation, membrane-less organelles, and biomolecular condensates

Abstract

Cellular biology is tightly linked to compartmentalization and formation of various biomolecular condensates and membrane-less organelles, which are typically liquid in nature and are not enclosed by a traditional lipid membrane. These liquid droplets are formed in response to changes in the cellular environment via tightly controlled and typically reversible liquid–liquid phase separation. They are many and can be found in various cellular compartments. The main constituents of membrane-less organelles are proteins (invariantly) and nucleic acids (often but not always). Many proteins found in these complex coacervates are intrinsically disordered, and their lack of stable structure is crucial for the reversible liquid–liquid phase separation–driven formation of these liquid droplets. Membrane-less organelles have numerous functions originating from proteins they contain. This chapter provides description of some major properties of proteins undergoing liquid–liquid phase separation, emphasizes the importance of intrinsic disorder for phase separation, and represents some reasons for the abundance of intrinsically disordered proteins in biomolecular condensates.