Toward a high-resolution mechanism of intrinsically disordered protein self-assembly.

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-β hypothesis, which focuses on the β-sheet interactions between the molecular surfaces constructed by multiple residues.