Remodeling of Lipid Vesicles into Cylindrical Micelles by α-Synuclein in an Extended α-Helical Conformation
Remodeling of Lipid Vesicles into Cylindrical Micelles by α-Synuclein in an Extended α-Helical Conformation
复制标题
DOI：
10.1074/jbc.m112.365817
复制
发表时间：
2012-08-24
影响因子：
4.8
通讯作者：
Steven, Alasdair C.
中科院分区：
文献类型：
--
作者：
Mizuno, Naoko;Varkey, Jobin;Steven, Alasdair C.
α-突触核蛋白（α S）是具有多种构象和相互作用的蛋白质。在溶液中天然解折叠后，α S在帕金森病的神经组织中以淀粉样蛋白形式积累，并在生理和病理条件下与细胞膜相互作用。在这里，我们使用冷冻电子显微镜结合电子顺磁共振（EPR）和其他技术来表征α S重塑囊泡的能力。在摩尔比为1：5比1：对于蛋白质/脂质（1-棕榈酰基-2-油酰基-sn-甘油基-3-磷酸甘油），大的球形囊泡转化为直径类似于50埃的圆柱形胶束。具有相同电荷（负）的其他脂质通常表现出类似的行为，尽管也产生150-500埃宽的双层管，这取决于脂质酰基链。在较高的蛋白质/脂质比下，形成直径为70-100埃的盘状颗粒。EPR数据表明，在圆柱形胶束，α S采用扩展的两亲性α-螺旋构象，其长轴与管轴对齐。所观察到的α S和胶束之间的几何关系表明，其长α-螺旋楔入膜的外小叶可能会导致曲率和脂质的各向异性分区，导致管形成。
alpha-Synuclein (alpha S) is a protein with multiple conformations and interactions. Natively unfolded in solution, alpha S accumulates as amyloid in neurological tissue in Parkinson disease and interacts with membranes under both physiological and pathological conditions. Here, we used cryoelectron microscopy in conjunction with electron paramagnetic resonance (EPR) and other techniques to characterize the ability of alpha S to remodel vesicles. At molar ratios of 1: 5 to 1: 40 for protein/lipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol), large spherical vesicles are converted into cylindrical micelles similar to 50 angstrom in diameter. Other lipids of the same charge (negative) exhibit generally similar behavior, although bilayer tubes of 150-500 angstrom in width are also produced, depending on the lipid acyl chains. At higher protein/lipid ratios, discoid particles, 70-100 angstrom across, are formed. EPR data show that, on cylindrical micelles, alpha S adopts an extended amphipathic alpha-helical conformation, with its long axis aligned with the tube axis. The observed geometrical relationship between alpha S and the micelle suggests that the wedging of its long alpha-helix into the outer leaflet of a membrane may cause curvature and an anisotropic partition of lipids, leading to tube formation.