How Intrinsically Disordered Proteins Modulate Biomolecular Condensates

ABSTRACT

Biomolecular condensates form various cellular membraneless organelles and play diverse biological functions as a result of their specific physicochemical properties. For example, biomolecular condensates are able to perceive changes in the external environment, regulate the cellular concentration of proteins, modulate different signaling pathways and selectively partition hub proteins as well as nucleic acids. Abnormal formation and changes of biomolecular condensates are closely related to human diseases, especially neurodegenerative diseases, cancers and viral diseases such as COVID-19. Intrinsically disordered proteins (IDPs) play key roles in the formation and regulation of biomolecular condensates. In this review, we analyze the roles that IDPs and small molecules play in biomolecular condensates formation and regulation, propose the possibility of rationally regulating biomolecular condensates through ligand design targeting IDPs, and discuss the challenges of understanding biomolecular condensate formation and regulation mechanisms and for discovering novel chemical compounds to modulate biomolecular condensates. © 2022 Chinese Academy of Sciences. All rights reserved.