Structural Rearrangement upon Fragmentation of the Stability Core of the ALS-Linked Protein TDP-43.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is the most common adult degenerative motor neuron disease. Experimental evidence indicates a direct role of transactive-response DNA-binding protein 43 (TDP-43) in the pathology of ALS and other neurodegenerative diseases. TDP-43 has been identified as a major component of cytoplasmic inclusions in patients with sporadic ALS; however, the molecular basis of the disease mechanism is not yet fully understood. Fragmentation within the second RNA recognition motif (RRM2) of TDP-43 has been observed in patient tissues and may play a role in the formation of aggregates in disease. To determine the structural and dynamical changes resulting from the truncation that could lead to aggregation and toxicity, we performed molecular dynamics simulations of the full-

SUBMITTER: Morgan BR 

PROVIDER: S-EPMC5550305 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature