Kiskis J, Horvath I, Wittung-Stafshede P, Rocha S
Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(8):75-81. doi: 10.17116/jnevro201811808175.
To analyze interactions between α-synuclein (αS) protein and lipids using biophysical methods.
Recombinant α-synuclein synthesized in prokaryotic cells was used. To characterize the interaction of αS with negatively charged vesicles of DOPS (1,2-dioleoyl-sn-glycero-3-phospho-L-serine, sodium salt) and DOPG (1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol), sodium salt) and the consequences of such interactions on αS amyloid formation, combined circular dichroism, fluorescence and imaging methods in vitro were applied.
Lipid head-group chemistry modulates αS interactions and also affects amyloid fiber formation. Pre-formed αS oligomers, typically present in a small amount in the αS starting material, acted as templates for linear growth of anomalous amyloid fibers in the presence of vesicles. At the same time, the remaining αS monomers were restricted from vesicle-mediated nucleation of amyloid fibers. Although not a dominant process in bulk experiments, this hidden αS aggregation pathway may be of importance in vivo.
运用生物物理方法分析α-突触核蛋白（αS）与脂质之间的相互作用。
使用在原核细胞中合成的重组α-突触核蛋白。为了表征αS与带负电荷的1,2-二油酰基-sn-甘油-3-磷酸-L-丝氨酸钠盐（DOPS）和1,2-二油酰基-sn-甘油-3-磷酸-（1'-外消旋甘油）钠盐（DOPG）囊泡的相互作用以及这种相互作用对αS淀粉样蛋白形成的影响，体外应用了圆二色性、荧光和成像相结合的方法。
脂质头部基团化学性质调节αS相互作用，也影响淀粉样纤维形成。预先形成的αS寡聚体通常在αS起始材料中少量存在，在囊泡存在的情况下作为异常淀粉样纤维线性生长的模板。同时，剩余的αS单体受到限制，无法进行囊泡介导的淀粉样纤维成核。尽管在大量实验中这不是主要过程，但这种隐藏的αS聚集途径在体内可能具有重要意义。
