Figure 1.

(A) Schematic representation of ataxin-3. Ataxin-3 contains an N-terminal Josephin domain, and three Ub-interacting motifs (UIMs) that flank a polyQ tract of variable length. In normal individuals, this tract can be anywhere from 10 to 51Q. In individuals with MJD, this tract has expanded to now contain >51Q. (B) Schematic representation of the interaction between ataxin-3 and CHIP. (1) CHIP contains an N-terminal tetratricopeptide repeat (TPR) domain and a C-terminal U-Box domain that confers CHIP with E3-Ub ligase activity. CHIP monoubiquitinates itself at lysine 2 (K2), which in turn facilitates the interaction between CHIP and ataxin-3. CHIP and ataxin-3 also interact directly although the nature of this interaction has yet to be characterized. (C) Schematic representation of the interaction between ataxin-3 and parkin. Parkin interacts directly with ataxin-3 via its N-terminal Ub-like domain (Ubl) that binds to the UIMs of ataxin-3, and through its inbetweenring-RING2 (IBR-RING2) domain binding to the Josephin domain of ataxin-3.