Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, University Paris-Saclay, 92296 Châtenay-Malabry, France.
Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
Sci Rep. 2016 Nov 30;6:37970. doi: 10.1038/srep37970.
Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson's disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young's modulus).
α-突触核蛋白（α-Syn）是一种由 140 个氨基酸组成的小突触前蛋白。其在中枢神经系统内的病理性细胞内聚集导致了Lewy 体的形成，Lewy 体是帕金森病（PD）的标志。在溶液中，纯α-Syn 采用固有无序的结构，并组装成纤维，其形态异质性很大，具体取决于其组装条件。我们最近建立了严格控制的实验条件，允许α-Syn 组装成高度均匀和纯的多晶型物。后者在形状、结构甚至功能特性上都存在差异。我们进行了高分辨率的 AFM 研究，并对纤维状α-Syn 的形状和热波动进行了统计分析，以计算其持久长度，从而进一步评估α-Syn 多晶型物的纳米力学性质。在这里，我们定量证明了由相同蛋白质（野生型α-Syn）组成的不同多晶型物在形态（高度、宽度和周期性）和物理性质（持久长度、弯曲刚性和轴向杨氏模量）方面存在显著差异。
