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[摘要]：Mutations in the E3 ubiquitin ligase Parkin are linked to Autosomal Recessive Juvenile Parkinsonism, including a cluster of pathogenic mutations in exon 2 that gives rise to Parkin's N-terminal ubiquitin-like domain (UblD). A study in this issue of The EMBO Journal reveals a new role for this domain, showing that the UblD engages in an intramolecular interaction with Parkin's C-terminal region to restrict autoubiquitination. Loss of this autoinhibitory mechanism in pathogenic variants renders Parkin constitutively active. Moreover, other proteins that bind to Parkin's UblD can also relieve autoinhibition, suggesting control by substrate-mediated activation. |
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