Haney Conor M, Petersson E James
Department of Chemistry, University of Pennsylvania, 213 South 34th Street, Philadelphia, PA 19104, USA.
Chem Commun (Camb). 2018 Jan 18;54(7):833-836. doi: 10.1039/c7cc08601f.
The neuronal protein α-synuclein (αS) plays a key role in Parkinson's disease, forming inclusions termed Lewy bodies and Lewy neurites. Recent improvements in cryo-electron diffraction and solid state NMR (ssNMR) have led to the elucidation of the structures of peptides derived from the αS fibril core and full-length human αS in fibrils. Despite the valuable insight offered by these methods, there are still several questions about the structures' relevance to pathological aggregates. Herein, we present fluorescence data collected in vitro under the conditions which fibrils are typically assembled. Our data suggest that, in solution, fibrils are largely structured as observed by ssNMR. However, we observe significant disparities in the αS N-terminus as compared to ssNMR data, which provide insight on its important role in αS aggregation and fibril structure.
神经元蛋白α-突触核蛋白（αS）在帕金森病中起关键作用，会形成名为路易小体和路易神经突的包涵体。近期低温电子衍射和固态核磁共振（ssNMR）技术的改进，使得源自αS纤维核心的肽段以及纤维状全长人αS的结构得以阐明。尽管这些方法提供了有价值的见解，但关于这些结构与病理性聚集体的相关性仍存在几个问题。在此，我们展示了在通常组装纤维的条件下体外收集的荧光数据。我们的数据表明，在溶液中，纤维在很大程度上如ssNMR所观察到的那样具有结构。然而，与ssNMR数据相比，我们在αS N端观察到显著差异，这为其在αS聚集和纤维结构中的重要作用提供了见解。
