Parkinson’s protein α-synuclein : membrane interactions and fibril structure

Kumar, P. (2017)

Doctoral Thesis

The thesis describes the use of electron paramagnetic resonance (EPR) spectroscopy, in continuous wave and pulse modes, to address the interaction of α-Synuclein (αS) with membranes and the aggregation of αS. The protein, αS, associated with Parkinson’s disease, plays its role by interacting with vesicles/membranes in nerve cells in the brain. We investigate, specifically, the interaction of αS with small unilamellar vesicles mimicking the inner mitochondrial membrane and the neuronal plasma membrane (chapter 2). Also, the influence of phosphorylation of αS at positions 87 and 129, mimicked by the mutations S87A, S129A (nonphosphorylated) and S87D, S129D (phosphorylated) on membrane binding is investigated (chapter 3). One of the peculiar properties of αS is to form amyloid fibrils. In the fibril, the protein chain of αS is folded into a β-sheet structure. We investigate how αS is folded in the fibrils (chapter 4 and 5). The chapter 6 focuses on peptides that help in membrane fusion. Using two small helical peptides, K and E, which act as zippers in the membrane-fusion model, we investigate the orientation of K and E in the zipper.

 

• α-Synuclein
• intrinsically disordered proteins
• Electron Paramagnetic Resonance
• αS-membrane interaction
• αS-phosphorylation
• Amyloid fibrils
• Fibril polymorphism
• Double Electron-Electron Resonance
• Membrane-fusion
• K/E-peptides

• All authors: Kumar, P.
• Supervisor: Groenen, Edgar J.J.
• Co-supervisor: Huber, Martina
• Committee: Hoyer, Wolfgang; Subramaniam, Vinod; Oosterkamp, Tjerk H.; Eliel, Eric R.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Institute of Physics (LION), Science, Leiden University
• Date: 2017-06-27
• Title of host publication: Casimir PhD Series
• ISBN (print): 9789085933014
• Name: 2017-17
• Sponsorship: FOM