Insight into the Folding and Dimerization Mechanisms of the N-Terminal Domain from Human TDP-43.

ABSTRACT: TAR DNA-binding protein 43 (TDP-43) is a 414-residue long nuclear protein whose deposition into intraneuronal insoluble inclusions has been associated with the onset of amyotrophic lateral sclerosis (ALS) and other diseases. This protein is physiologically a homodimer, and dimerization occurs through the N-terminal domain (NTD), with a mechanism on which a full consensus has not yet been reached. Furthermore, it has been proposed that this domain is able to affect the formation of higher molecular weight assemblies. Here, we purified this domain and carried out an unprecedented characterization of its folding/dimerization processes in solution. Exploiting a battery of biophysical approaches, ranging from FRET to folding kinetics, we identified a head-to-tail arrangement of the monomers wit

SUBMITTER: Vivoli-Vega M 

PROVIDER: S-EPMC7504384 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature