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Publication Abstract from PubMed

Mutations in the Parkin gene are responsible for an autosomal recessive form of Parkinson's disease. The parkin protein is a RING-In-Between-RING (RBR) E3 ubiquitin ligase, which exhibits low basal activity. Here, we describe the crystal structure of full-length parkin. The structure shows parkin in an auto-inhibited state and provides insight into how it is activated. RING0 occludes the ubiquitin acceptor site Cys431 in RING2, whereas a repressor element of parkin (REP) 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.

Structure of Parkin Reveals Mechanisms for Ubiquitin Ligase Activation.,Trempe JF, Sauve V, Grenier K, Seirafi M, Tang MY, Menade M, Al-Abdul-Wahid S, Krett J, Wong K, Kozlov G, Nagar B, Fon EA, Gehring K Science. 2013 May 9. PMID:23661642^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.