Single-molecule nanopore dielectrophoretic trapping of a-synuclein with lipid membranes
Single-molecule nanopore dielectrophoretic trapping of a-synuclein with lipid membranes
复制标题
脂膜单分子纳米孔介电泳捕获α-突触核蛋白
DOI：
10.1016/j.xcrp.2022.101243
复制
发表时间：
2023
影响因子：
8.9
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Wu J
脂质-α-突触核蛋白（α-Syn）相互作用在帕金森病的发病机制中起着至关重要的作用。在这里，我们研究了α-Syn在α-溶血素（αHL）单纳米孔中的脂质结合和非结合动力学。在施加的电压下，由于介电泳力，工程化的α-Syn序列可以被捕获在纳米孔处。通过对阻断电流幅值和停留时间的解释，可以观察到α-Syn在孔膜连接处的构象转换事件。这允许进一步分析α-Syn构象动力学。我们研究了疾病相关的金属离子（Cu ~（2+）、Zn ~（2+））如何调节α-Syn在膜和孔界面的动力学以及α-螺旋肽模拟物如何稳定α-Syn的螺旋构象。这些研究有助于我们理解α-Syn、脂质膜和金属离子相互作用的复杂性，并且在使用肽模拟物时，提出了一种对抗α-Syn毒性和聚集的新策略。
The lipid-α-Synuclein (α-Syn) interaction plays a crucial role in the pathogenesis of Parkinson's disease. Here, we investigate the lipid-binding and -unbinding kinetics of α-Syn in an α-hemolysin (αHL) single nanopore. Under an applied voltage, an engineered α-Syn sequence can be trapped at the nanopore due to the dielectrophoretic force. The conformational switch events of α-Syn can be observed at the pore-membrane junction through the interpretation of blockade current amplitudes and dwell time. This allows further analysis of α-Syn conformational dynamics. We study how disease-associated metal ions (Cu2+, Zn2+) modulate the dynamics of α-Syn at the interface of the membranes and pore and how α-helical peptidomimetics stabilize the helical conformation of α-Syn in a lipidic environment. These studies aid our understanding of the complexity of the interaction of α-Syn, lipid membranes, and metal ions, and in using peptidomimetics, a new strategy against α-Syn toxicity and aggregation is advanced.