DNA-Mediated Formation of Phase-Separated Coacervates of the Nucleic Acid-Binding Domain of TAR DNA-Binding Protein (TDP-43) Prevents Its Amyloid-Like Misfolding.

Sequestration of protein molecules and nucleic acids to stress granules is one of the most promising strategies that cells employ to protect themselves from stress. In vitro, studies suggest that the nucleic acid-binding domain of TDP-43 (TDP-43) undergoes amyloid-like aggregation to β-sheet-rich structures in low pH stress. In contrast, we observed that the TDP-43 undergoes complex coacervation in the presence of ssDNA to a dense and light phase, preventing its amyloid-like aggregation.