Site-specific methionine oxidation alters structure and phase separation of TDP-43 C-terminal domain.

ABSTRACT: TAR DNA binding protein 43 (TDP-43), a key protein linked to ALS pathology, undergoes phase separation and forms functional assemblies via condensation within cells. The conserved region (CR) within its C-terminal domain (CTD) mediates self-assembly through helix-helix interactions, while the flanking intrinsically disordered regions (IDRs) contribute to phase separation through transient interactions involving aromatic and hydrophobic residues. The CTD contains ten methionine residues distributed equally between these regions, making it particularly susceptible to oxidative modifications. While methionine oxidation is known to impair phase separation, neither the precise mechanism nor the specific contribution of methionines in the CR compared to the IDRs has been determined. Here, we com

SUBMITTER: Ozguney B 

PROVIDER: S-EPMC12724696 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature