PhaseProtein

Phaseprotein is a descriptive term used to refer to proteins that drive phase separation in cells, forming dynamic biomolecular condensates by liquid-liquid phase separation. These condensates organize cellular biochemistry by concentrating specific factors and substrates and can assemble and disperse in response to cellular conditions, enabling rapid and reversible control of biochemical reactions.

Most phaseproteins have intrinsically disordered regions (IDRs) and low-complexity domains that enable multivalent interactions. They often contain RNA-binding domains and other interaction motifs, and their phase behavior can be influenced by RNA, post-translational modifications, and changes in concentration, temperature, ionic strength, or crowding inside the cell.

In cells, phaseproteins contribute to spatial and temporal organization of processes such as transcriptional regulation, RNA processing and metabolism, stress responses, and signaling. The resulting condensates—nucleoli, stress granules, P bodies, and other membraneless bodies—are typically dynamic, allowing components to exchange with the surrounding milieu and respond to cellular needs.

Dysregulation of phaseproteins can be associated with disease. Aberrant phase separation can lead to the formation of irreversible or pathological aggregates, and genetic mutations or abnormal post-translational modification patterns can alter the propensity for condensation. Research often links such changes to neurodegenerative and other disorders.

Research and methods: The study of phaseproteins uses in vitro reconstitution, live-cell imaging, fluorescence recovery after photobleaching (FRAP), and increasingly optogenetic approaches to control condensation. The term phaseprotein remains a descriptive concept rather than a formal protein family, reflecting a functional property rather than a fixed classification.

Impact and future directions: Understanding phaseproteins informs basic cell biology, disease mechanisms, and the design of synthetic condensates for biotechnology and therapeutic strategies.