Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation.

ABSTRACT: Phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients is located in the low-complexity domain (LCD), the same domain that has been shown to be critical for TDP-43 liquid-liquid phase separation (LLPS). However, the effect of these LCD phosphorylation sites on TDP-43 LLPS has been largely unexplored, and any work that has been done has mainly focused on sites nea

SUBMITTER: Haider R 

PROVIDER: S-EPMC10870169 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature