Mode of substrate recognition by the Josephin domain of ataxin-3, which has an endo-type deubiquitinase activity

Ataxin‐3, which is encoded by a gene that has been associated with Machado–Joseph disease, contains a catalytic N‐terminal Josephin domain with deubiquitinase activity. Here, we show that the Josephin domain of ataxin 3 catalyzes endo‐type cleavage of Lys48‐linked polyubiquitin. Furthermore, NMR data obtained following site‐specific paramagnetic spin labeling of Lys48‐linked di‐ubiquitin revealed that both ubiquitin units interact with the...