J Phys Chem B 2021 Apr 9;125(15):3781-3789. Epub 2021 Apr 9.
Laboratory of Protein Conformation and Dynamics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
Aggregated TAR DNA-binding protein 43 (TDP-43) forms the cytoplasmic hallmarks associated with patients suffering from amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin. Under normal conditions, TDP-43 is a 414-amino acid protein; however, aggregates are enriched with N-terminal truncations which contain residues 267-414, known as the C-terminal domain of TDP-43 (TDP-43). To gain residue-specific information on the aggregation process of TDP-43, we created three single-Trp containing mutants (W385F/W412F, W334F/W412F, and W334F/W385F) by substituting two of the three native Trp residues with Phe, yielding fluorescent probes at W334, W385, and W412, respectively. Read More