ABSTRACT
Membraneless organelles formed via the self-assembly of intrinsically disordered proteins (IDPs) play a crucial role in regulating various physiological functions. Elucidating the mechanisms behind IDP self-assembly is of great interest not only from a biological perspective but also for understanding how amino acid mutations in IDPs contribute to the development of neurodegenerative diseases and other disorders. Currently, two proposed mechanisms explain IDP self-assembly: (1) the sticker-and-spacer framework, which considers amino acid residues as beads to simulate the intermolecular interactions, and (2) the cross-ß hypothesis, which focuses on the ß-sheet interactions between the molecular surfaces constructed by multiple residues. This review explores the advancement of new models that provide higher resolution insights into the IDP self-assembly mechanism based on new findings obtained from structural studies of IDPs.
