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Simultaneous IR‐Spectroscopic Observation of α‐Synuclein, Lipids, and Solvent Reveals an Alternative Membrane‐Induced Oligomerization Pathway
Author(s) -
Fallah Mohammad A.,
Gerding Hanne R.,
Scheibe Christian,
Drescher Malte,
Karreman Christiaan,
Schildknecht Stefan,
Leist Marcel,
Hauser Karin
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700355
Subject(s) - membrane , chemistry , biophysics , protein aggregation , biochemistry , biology
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.