Electrochemical and surface analysis of interactions between Cu(II) and Zn(II) metal ions with TDP-43 protein immobilized on gold surfaces

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss in function within the motor neurons. Elevated copper (II) (Cu(II)) levels have been reported in ALS cases and may contribute to oxidative stress via reactive oxygen species. Cu(II) interactions with other proteins associated with ALS have been investigated, however, the effects of metallation on transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) are less known. Normal TDP-43 regulates transcription in the nucleus and cytoplasm, however, in diseased cells, TDP-43 misfolds and loses function. Here, we present an electrochemical and surface study of the interactions between the full-length TDP-43 and Cu(II) ions. The electrochemical signal was observed at 0.18 V vs Ag/AgCl for the TDP-43 immobilized on gold (Au) surface (TDP-43-Au) after Cu(II) binding due to the Cu(II)/(I) redox couple. Competitive and displacement studies with Zinc(II) ions revealed that TDP-43-Au films preferentially bind Cu(II), which may have biological significance.