| First Author | Trempe JF | Year | 2009 |
| Journal | Mol Cell | Volume | 36 |
| Issue | 6 | Pages | 1034-47 |
| PubMed ID | 20064468 | Mgi Jnum | J:156815 |
| Mgi Id | MGI:4421462 | Doi | 10.1016/j.molcel.2009.11.021 |
| Citation | Trempe JF, et al. (2009) SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination. Mol Cell 36(6):1034-47 |
| abstractText | 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. |
