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

  • Author / Creator
    Morrison, Melissa A
  • 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

  • Subjects / Keywords
  • Graduation date
    2013-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3KD1QT41
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Biochemistry
  • Supervisor / co-supervisor and their department(s)
    • M. Joanne Lemieux (Biochemistry
  • Examining committee members and their departments
    • Joseph Casey (Biochemistry)
    • Larry Fliegel (Biochemistry)
    • Bernie Lemire (Biochemistry)
    • Simonetta Sipione (Pharmocology)
    • M. Joanne Lemieux (Biochemistry)