Fig. 6

The CHIP p.Glu278fs mutation may impair α-synuclein and tau degradation by disrupting the E2-U-box interaction, thereby promoting ataxia progression. CHIP targets misfolded proteins for proteasome degradation. Under normal conditions, CHIP binds to E2 ligase to form an HSP70 chaperone complex and initiate ubiquitination of the misfolded protein. Under the ataxia condition, the interaction between CHIP and its specific E2 ligase is inhibited, which disrupts CHIP’s E3 ligase activity