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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 …