Figure 8.

Model for Parkin activation. In the physiological state (left), Parkin is autoinhibited and activated by effectors, which may in turn bind true Parkin substrates. The C-terminal RING regions recruit E2, with an additional interaction between the thioester charged ubiquitin on E2 and the PUB motif in Parkin. This may enhance substrate ubiquitination and/or Parkin autoubiquitination. In the disease state (right), a constitutively active Parkin autoubiquitinates and is targeted for proteasomal degradation.