An Intramolecular Salt Bridge Linking TDP43 RNA Binding, Protein Stability, and TDP43-Dependent Neurodegeneration (Cell Reports)

Flores et al. uncover essential roles for an intramolecular salt bridge in the function of TDP43, an RNA binding protein implicated in neurodegenerative diseases. Salt bridge interruption attenuates TDP43 RNA binding affinity and specificity, destabilizes the protein, and prevents TDP43-mediated neurotoxicity arising from misprocessing of ribosomal and mitochondrial transcripts.