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Parkin, A Top Level Manager in the Cell’s Sanitation Department
Rankin, Carolyn A. Roy, Ambrish Zhang, Yang Richter, Mark
Rankin, Carolyn A.
Roy, Ambrish
Zhang, Yang
Richter, Mark
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Abstract
Parkin belongs to a class of multiple RING domain proteins designated as RBR (RING, in between RING, RING) proteins. In this review we examine what is known regarding the structure/function relationship of the Parkin protein. Parkin contains three RING domains plus a ubiquitin-like domain and an in-between-RING (IBR) domain. RING domains are rich in cysteine amino acids that act as ligands to bind zinc ions. RING domains may interact with DNA or with other proteins and perform a wide range of functions. Some function as E3 ubiquitin ligases, participating in attachment of ubiquitin chains to signal proteasome degradation; however, ubiquitin may be attached for purposes other than proteasome degradation.
It was determined that the C-terminal most RING, RING2, is essential for Parkin to function as an E3 ubiquitin ligase and a number of substrates have been identified. However, Parkin also participates in a number of other fiunctions, such as DNA repair, microtubule stabilization, and formation of aggresomes. Some functions, such as participation in a multiprotein complex implicated in NMDA activity at the post synaptic density, do not require ubiquitination of substrate molecules. Recent observations of RING proteins suggest their function may be regulated by zinc ion binding. We have modeled the three RING domains of Parkin and have identified a new set of RING2 ligands. This set allows for binding of two rather than just one zinc ion, opening the possibility that the number of zinc ions bound acts as a molecular switch to modulate Parkin function.
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Date
2011
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Publisher
Bentham
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Keywords
Parkin, Zinc-binding, Domains, E3 ligase ubiquitination
Citation
Rankin, Carolyn A.; Roy, Ambrish; Zhang, Yang; Richter, Mark. Parkin, A Top Level Manager in the Cell’s Sanitation Department. The Open Biochemistry Journal, 2011, 5, 9-26. http://dx.doi.org/10.2174/1874091X01105010009