Structural dissection of TDP-43

TAR DNA-binding protein of 43 kDa (TDP-43) is an essential RNA-binding protein, self-assembles into prion-like aggregates, and is known to be the structural hallmark of amyotrophic lateral sclerosis and frontotemporal dementia and other neurodegenerative diseases. An in-depth study of the TDP-43 structure, self-association, and effect of mutations is critical to develop therapeutic strategies against TDP-43 proteinopathies. Recent structural studies of TDP-43 offer an extensive insight toward understanding the molecular mechanisms of TDP-43 function. These lay the foundation for a better molecular understanding of both the physiological and pathological functions underlying neurodegenerative diseases. In this chapter, we are discussing the structural characteristics of TDP-43 domains and providing insights that how these structures are associated with the physiological and pathological functions of TDP-43.