Mutations in the parkin gene are responsible for a common inherited form of 
Parkinson's disease (PD). Parkin is a RING-type E3 ubiquitin ligase with an 
N-terminal ubiquitin-like domain (Ubl). We report here that the parkin Ubl binds 
SH3 domains from endocytic BAR proteins such as endophilin-A with an affinity 
comparable to proline-rich domains (PRDs) from well-established SH3 partners. 
The NMR structure of the Ubl-SH3 complex identifies the PaRK extension, a unique 
C-terminal motif in the parkin Ubl required for SH3 binding and for 
parkin-mediated ubiquitination of endophilin-A in vitro. In nerve terminals, 
conditions that promote phosphorylation enhance the interaction between parkin 
and endophilin-A and increase the levels of ubiquitinated proteins within 
PRD-associated synaptic protein complexes in wild-type but not parkin knockout 
brain. The findings identify a pathway for the recruitment of synaptic 
substrates to parkin with the potential to explain the defects in synaptic 
transmission observed in recessive forms of PD.