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Permanent link (DOI): https://doi.org/10.7939/R3KD1QT41

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Understanding the Role of Rhomboid Proteases and Their Substrates in Parkinson's Disease Open Access

Descriptions

Other title
Subject/Keyword
Parkinson's Disease
PARL
Rhomboid Protease
PINK1
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Morrison, Melissa A
Supervisor and department
M. Joanne Lemieux (Biochemistry
Examining committee member and department
Larry Fliegel (Biochemistry)
Bernie Lemire (Biochemistry)
M. Joanne Lemieux (Biochemistry)
Simonetta Sipione (Pharmocology)
Joseph Casey (Biochemistry)
Department
Department of Biochemistry
Specialization

Date accepted
2013-06-28T09:11:13Z
Graduation date
2013-11
Degree
Master of Science
Degree level
Master's
Abstract
PINK1 (Phosphatase Tensin homologue (PTEN)-Induced Kinase) is a neuroprotective kinase involved in mitochondrial dynamics. It is composed of an N-terminal mitochondrial targeting sequence, transmembrane domain and C-terminal kinase domain. PINK1 is imported into mitochondria and anchored into the IMM, where it is rapidly cleaved by intramembrane rhomboid protease, PARL (Presenilin-Associated Rhomboid-Like). Mutations that prevent cleavage or signaling events of the kinase domain result in Parkinson’s disease. This thesis aims to assess the structure of the PINK1 membrane domain to further understand its interactions with PARL. We predict that Parkinson’s disease mutations found in the transmembrane domain may alter the secondary structure to prevent cleavage of PINK1 by PARL. The PINK1 TM domain was expressed and purified in E. coli and been analyzed by nuclear magnetic resonance (NMR). An expression and screening system has been developed in Pichia pastoris, which has been used to design a preliminary expression regimen for PARL
Language
English
DOI
doi:10.7939/R3KD1QT41
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Brooks, C. L., Morrison, M. and Joanne Lemieux, M. (2013), Rapid expression screening of eukaryotic membrane proteins in Pichia pastoris. Protein Science, 22: 425–433

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File author: Melissa Morrison
Page count: 159
File language: en-US
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