Phe-Gly motifs drive fibrillization of TDP-43's prion-like domain condensates.

ABSTRACT: Transactive response DNA-binding Protein of 43 kDa (TDP-43) assembles various aggregate forms, including biomolecular condensates or functional and pathological amyloids, with roles in disparate scenarios (e.g., muscle regeneration versus neurodegeneration). The link between condensates and fibrils remains unclear, just as the factors controlling conformational transitions within these aggregate species: Salt- or RNA-induced droplets may evolve into fibrils or remain in the droplet form, suggesting distinct end point species of different aggregation pathways. Using microscopy and NMR methods, we unexpectedly observed in vitro droplet formation in the absence of salts or RNAs and provided visual evidence for fibrillization at the droplet surface/solvent interface but not the droplet interio

SUBMITTER: Pantoja-Uceda D 

PROVIDER: S-EPMC8109789 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature