Molecular defects of the dystonia-causing torsinA mutation

The Delta GAG deletion mutation in DYTI, causing a loss of a glutamic acid near the carboxyl terminus of torsinA protein (torsinA Delta E), is dominantly inherited and tends to result in a severe generalized form of dystonia with childhood onset. We have used a yeast two-hybrid interaction assay to examine torsinA and its mutant torsinA Delta E interactions. Our data showed that torsinA monomers are capable of interacting with themselves and that mutant torsinA Delta E fails to interact with itself or with torsinA. We also demonstrated that purified torsinA protein is an ATPase, which forms a multimeric complex in vitro and that the Delta GAG mutation disrupts the formation of multimeric complex and decreases torsinA's ATPase activity.