Structure of parkin reveals mechanisms for ubiquitin ligase activation
Science, 2013•science.org
Mutations in the PARK2 (parkin) gene are responsible for an autosomal recessive form of
Parkinson's disease. The parkin protein is a RING-in-between-RING E3 ubiquitin ligase that
exhibits low basal activity. We describe the crystal structure of full-length rat parkin. The
structure shows parkin in an autoinhibited state and provides insight into how it is activated.
RING0 occludes the ubiquitin acceptor site Cys431 in RING2, whereas a repressor element
of parkin binds RING1 and blocks its E2-binding site. Mutations that disrupted these …
Parkinson's disease. The parkin protein is a RING-in-between-RING E3 ubiquitin ligase that
exhibits low basal activity. We describe the crystal structure of full-length rat parkin. The
structure shows parkin in an autoinhibited state and provides insight into how it is activated.
RING0 occludes the ubiquitin acceptor site Cys431 in RING2, whereas a repressor element
of parkin binds RING1 and blocks its E2-binding site. Mutations that disrupted these …
Mutations in the PARK2 (parkin) gene are responsible for an autosomal recessive form of Parkinson’s disease. The parkin protein is a RING-in-between-RING E3 ubiquitin ligase that exhibits low basal activity. We describe the crystal structure of full-length rat parkin. The structure shows parkin in an autoinhibited state and provides insight into how it is activated. RING0 occludes the ubiquitin acceptor site Cys431 in RING2, whereas a repressor element of parkin binds RING1 and blocks its E2-binding site. Mutations that disrupted these inhibitory interactions activated parkin both in vitro and in cells. Parkin is neuroprotective, and these findings may provide a structural and mechanistic framework for enhancing parkin activity.
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