Repulsive vs Attractive Crowding Distinctly Regulate TDP-43 Condensates through Region-specific Structural Dynamics.

ABSTRACT: TAR DNA-binding protein 43 (TDP-43) is crucial for RNA processing and nucleocytoplasmic transport, and its pathological aggregation marks neurodegenerative disease. The intrinsically disordered, prion-like C-terminal domain (CTD) drives liquid-liquid phase separation (LLPS). Using residue-level coarse-grained simulations, we systematically examine how distinct macromolecular crowding environments, including repulsive (steric) and attractive (interaction-based) crowding conditions, influence the phase behavior and internal organization of TDP-43 CTD condensates. Both crowder types preserve correlations between single-chain compaction, dimerization propensity, and macroscopic phase separation, yet act through different mechanisms: repulsive crowders promote condensation via excluded-volume e

SUBMITTER: Zhang G 

PROVIDER: S-EPMC12569666 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature