Simultaneous IR‐Spectroscopic Observation of α‐Synuclein, Lipids, and Solvent Reveals an Alternative Membrane‐Induced Oligomerization Pathway. (2nd November 2017)

• Record Type: Journal Article
• Authors: Fallah, Mohammad A.; Gerding, Hanne R.; Scheibe, Christian; Drescher, Malte; Karreman, Christiaan; Schildknecht, Stefan; Leist, Marcel; Hauser, Karin
• Is Part Of: Chembiochem. Volume 18:Number 23(2017)
• Page Start: 2312
• Page End: 2316
• Publication Date: 2017-11-02
• Subjects: aggregation -- alpha-synuclein -- ATR-FTIR -- protein–membrane interaction -- solid-supported lipid bilayers; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700355
• Languages: English
• ISSNs: 1439-4227

Abstract

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. Abstract : Aggregation of Parkinson's‐associated proteins : The presence of a membrane changes the oligomerization pathway of Parkinson's‐associated intrinsically disordered protein (IDP) α‐synuclein from that observed in solution. Membrane remodeling and disruption are caused not by the final aggregates, but by specific membrane–aggregate interaction.