Simultaneous IR‐Spectroscopic Observation of α‐Synuclein,Lipids, and Solvent Reveals an Alternative Membrane‐Induced Oligomerization Pathway |
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| Authors: | Dr. Mohammad A. Fallah Hanne R. Gerding Christian Scheibe Prof. Dr. Malte Drescher Dr. Christiaan Karreman Dr. Stefan Schildknecht Prof. Dr. Marcel Leist Prof. Dr. Karin Hauser |
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| Affiliation: | 1. Department of Chemistry, University of Konstanz, Konstanz, Germany;2. Department of Biology, University of Konstanz, Konstanz, Germany |
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| Abstract: | The intrinsically disordered protein α‐synuclein (αS), a known pathogenic factor for Parkinson's disease, can adopt defined secondary structures when interacting with membranes or during fibrillation. The αS–lipid interaction and the implications of this process for aggregation and damage to membranes are still poorly understood. Therefore, we established a label‐free infrared (IR) spectroscopic approach to allow simultaneous monitoring of αS conformation and membrane integrity. IR showed its unique sensitivity for identifying distinct β‐structured aggregates. A comparative study of wild‐type αS and the naturally occurring splicing variant αS Δexon3 yielded new insights into the membrane's capability for altering aggregation pathways. |
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| Keywords: | aggregation alpha-synuclein ATR-FTIR protein– membrane interaction solid-supported lipid bilayers |
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