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Custom Vector Construction | … ) with a hexahistidine tag (His 6 ) at the N-terminal was codon optimized, synthesized, and cloned, in a pET-15b vector between the NcoI and BamHI restriction sites, from GenScript. … | Get A Quote |
Cellular stress is a major cause of neurodegenerative diseases. In particular, in amyotrophic lateral sclerosis (ALS), around 90% of the cases are believed to occur due to aggregation and misfolding of TDP-43 protein in neurons due to aging and chronic environmental stress. However, the physicochemical basis of how TDP-43 senses the change in solvation conditions during stress and misfolds remains very poorly understood. We show here that the full-length human TDP-43 can exist in equilibrium with multiple structural states. The equilibrium between these states is highly sensitive to changes in solvation conditions. We show that upon thermal and pH stress, amyloidogenic oligomers can form amyloid-like fibrils. H... More