Fallah Mohammad A, Gerding Hanne R, Scheibe Christian, Drescher Malte, Karreman Christiaan, Schildknecht Stefan, Leist Marcel, Hauser Karin
Department of Chemistry, University of Konstanz, Universitätsstrasse 10, 78457, Konstanz, Germany.
Department of Biology, University of Konstanz, Universitätsstrasse 10, 78457, Konstanz, Germany.
Chembiochem. 2017 Dec 5;18(23):2312-2316. doi: 10.1002/cbic.201700355. Epub 2017 Nov 2.
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.
内在无序蛋白α-突触核蛋白（αS）是已知的帕金森病致病因子，在与膜相互作用或纤维化过程中可形成特定的二级结构。αS与脂质的相互作用以及该过程对膜聚集和损伤的影响仍知之甚少。因此，我们建立了一种无标记红外（IR）光谱方法，以同时监测αS构象和膜完整性。红外光谱显示出其在识别不同β结构聚集体方面的独特灵敏度。对野生型αS和天然存在的剪接变体αS Δexon3的比较研究，为膜改变聚集途径的能力提供了新的见解。
