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Full-Text Articles in Biochemistry
The Study Of The Structure And Dynamics Of Parkin Activation, Elaine Aisha Freeman
The Study Of The Structure And Dynamics Of Parkin Activation, Elaine Aisha Freeman
Electronic Thesis and Dissertation Repository
Parkin is an RBR E3 ubiquitin ligase that has been implicated in both sporadic and familial Parkinson’s disease. Upon mitochondrial damage, parkin is activated step-wise to recruit and ligate ubiquitin to a substrate on the outer mitochondrial membrane. Disruption of this activation and ligation cascade is hypothesized to result in neuronal death related to Parkinson’s disease.
While structures of parkin for a number of these activation states exist, it is important to note they are not of full-length human parkin. These structures are often truncated and come from various non-human species to eliminate important, yet hard to quantify structural elements. …
New Perspectives On Phosphorylation State In The Parkin Ubiquitination Cascade, Karen Dunkerley
New Perspectives On Phosphorylation State In The Parkin Ubiquitination Cascade, Karen Dunkerley
Electronic Thesis and Dissertation Repository
The RBR E3 ligase parkin is recruited to the outer mitochondrial membrane (OMM) during oxidative stress where it becomes activated and ubiquitinates numerous proteins. Parkin activation involves binding of a phosphorylated ubiquitin (pUb), followed by phosphorylation of parkin itself, both mediated by the OMM kinase, PINK1. However, targeted mitochondrial proteins have little structural or sequence similarity, with the commonality between substrates being proximity to the OMM. The objective of this thesis was to identify the molecular consequences of parkin phosphorylation, interaction with pUb and how this promotes ubiquitination activity of known Ub-acceptor proteins and parkin itself.
The three-dimensional structure of …