Conserved region of human TDP-43 is structurally similar to membrane binding protein FARP1 and protein chaperons BAG6 and CYP33.

Abstract

Transactive response DNA-binding protein of 43 KDa (TDP-43) is important for RNA metabolism in all animals and in humans is involved in neuromuscular diseases. Full-length TDP-43 is prone to oligomerization and misfolding what renders difficult its characterization. We report that TDP-43 domains are structurally similar to lipid binding protein FARP1 and protein chaperons BAG6 and CYP33. Sequence analysis suggests putative lipid binding sites throughout TDP-43 and in vitro thioflavin T fluorescence assays show that cholesterol and phosphatidylcholine affect fibrillation of recombinant TDP-43 fragments. Our findings suggest that TDP-43 can bind lipids directly and it may contribute to its own chaperoning.