Protein Language Model Identifies Disordered, Conserved Motifs Implicated in Phase Separation.

ABSTRACT: Intrinsically disordered regions (IDRs) play a critical role in phase separation and are essential for the formation of membraneless organelles (MLOs). Mutations within IDRs can disrupt their multivalent interaction networks, altering phase behavior and contributing to various diseases. Therefore, examining the evolutionary constraints of IDRs provides valuable insights into the relationship between protein sequences and phase separation. In this study, we utilized the ESM2 protein language model to map the residue-level mutational tolerance landscapes landscape of IDRs. Our findings reveal that IDRs, particularly those actively participating in phase separation, contain conserved amino acids. This conservation is evident through mutational constraints predicted by ESM2 and supported by di

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12330624 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature