α-Synuclein Interaction with Membranes Public Deposited

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  • March 19, 2019
Creator
  • Zigoneanu, Imola G.
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • The association of α-synuclein with membranes appears to be an important factor in Parkinson's disease. My dissertation research was focused on understanding the interactions of the protein with artificial membranes, the extracellular plasma membrane, and intracellular membranes. Fluorescence and nuclear magnetic resonance spectroscopy were used to monitor these interactions. Large unillamelar vesicles with a composition similar to mitochondrial membranes were studied. Cardiolipin, present mainly in the inner mitochondrial membrane, is key for protein binding, and reducing the amount of cardiolipin decreases binding. The nature of cardiolipin's acyl chains is also important; cardiolipin with chains containing one double bond interact more strongly than those with chains having two double bonds or saturated acyl chains. This finding is physiologically relevant for Parkinson's disease because cardiolipin containing fatty acids with one double bond are the most abundant phospholipid in the brain. The affinity of α-synuclein for plasma membrane was tested, and only N-terminal region of the protein binds. Also, 19F NMR proved useful for monitoring the interactions of proteins and fused peptide-proteins with the plasma membrane. Information on protein interactions with intracellular membranes reveals that the N-terminal region may be cleaved in cells, but further studies are needed to confirm this idea.
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  • In Copyright
Advisor
  • Pielak, Gary J.
Degree
  • Doctor of Philosophy
Graduation year
  • 2011
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