Associations between the 140 amino acid protein alpha-synuclein (asyn) and presynaptic vesicles may play a role in maintaining synaptic plasticity and neurotransmitter release. These physiological processes may involve disruption and fusion of vesicles, arising from interactions between specific regions of asyn, including the highly basic N-terminal domain, and the surface of vesicles. This work investigates whether asyn affects the integrity of model unilamellar vesicles of varying size and phospholipid composition, by monitoring paramagnetic Mn(2+)-induced broadening of peaks in the (31)P nuclear magnetic resonance spectrum of the lipid head groups. It is shown that asyn increases the permeability to Mn(2+) of both large (200 nm diameter) and small (50 nm diameter) vesicles composed of zwitterionic phosphatidylcholine and anionic phosphatidylglycerol at protein/lipid molar ratios as low as 1:2000. Further experiments on peptides corresponding to sequences in the N-terminal (10-48), C-terminal (120-140) and central hydrophobic (71-82) regions of asyn suggest that single regions of the protein are capable of permeabilizing the vesicles to varying extents. Electron micrographs of the vesicles after addition of asyn indicate that the enhanced permeability is coupled to large-scale disruption or fusion of the vesicles. These results indicate that asyn is able to permeabilize phospholipid vesicles at low relative concentrations, dependent upon the properties of the vesicles. This could have implications for asyn playing a role in vesicle synthesis, maintenance and fusion within synapses.

中文翻译：

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α-突触核蛋白对磷脂囊泡完整性的影响：使用31P NMR和电子显微镜的研究。

140个氨基酸的蛋白质α-突触核蛋白（asyn）与突触前囊泡之间的关联可能在维持突触可塑性和神经递质释放中起作用。这些生理过程可能涉及囊泡的破坏和融合，这是由异步蛋白的特定区域（包括高度碱性的N端结构域）与囊泡表面之间的相互作用引起的。这项工作通过监测顺磁Mn（2+）诱导脂质头基团的（31）P核磁共振波谱中的峰变宽，研究了asyn是否会影响大小和磷脂成分不同的模型单层囊泡的完整性。结果表明，在蛋白质/脂质摩尔比低至1：2000的情况下，由两性离子磷脂酰胆碱和阴离子磷脂酰甘油组成的大囊泡（直径200 nm）和小囊泡（直径50 nm）对Mn（2+）的渗透性增加。对与asyn的N端（10-48），C端（120-140）和中央疏水（71-82）区域中的序列相对应的肽进行的进一步实验表明，该蛋白质的单个区域能够渗透小泡在不同程度上。添加asyn后囊泡的电子显微照片表明，增强的渗透性与囊泡的大规模破坏或融合相关。这些结果表明，取决于囊泡的性质，asyn能够以低相对浓度透化磷脂囊泡。