Choo-Smith L P, Garzon-Rodriguez W, Glabe C G, Surewicz W K
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
J Biol Chem. 1997 Sep 12;272(37):22987-90. doi: 10.1074/jbc.272.37.22987.
The interaction of Alzheimer's Abeta peptide and its fluorescent analogue with membrane vesicles was studied by spectrofluorometry, Congo Red binding, and electron microscopy. The peptide binds selectively to the membranes containing gangliosides with a binding affinity ranging from 10(-6) to 10(-7) M depending on the type of ganglioside sugar moiety. This interaction appears to be ganglioside-specific as under our experimental conditions (neutral pH, physiologically relevant ionic strength), no Abeta binding was observed to ganglioside-free membranes containing zwitterionic or acidic phospholipids. Importantly, the addition of ganglioside-containing vesicles to the peptide solution dramatically accelerates the rate of fibril formation as compared with that of the peptide alone. The present results strongly suggest that the membrane-bound form of the peptide may act as a specific "template" (seed) that catalyzes the fibrillogenesis process in vivo.
通过荧光光谱法、刚果红结合法和电子显微镜研究了阿尔茨海默病β淀粉样肽及其荧光类似物与膜囊泡的相互作用。该肽选择性地结合含有神经节苷脂的膜，其结合亲和力范围为10^(-6)至10^(-7) M，这取决于神经节苷脂糖部分的类型。在我们的实验条件下（中性pH、生理相关离子强度），这种相互作用似乎具有神经节苷脂特异性，未观察到该β淀粉样肽与含有两性离子或酸性磷脂的无神经节苷脂膜结合。重要的是，与单独的肽相比，向肽溶液中添加含神经节苷脂的囊泡显著加速了原纤维形成的速率。目前的结果有力地表明，肽的膜结合形式可能作为一种特异性“模板”（种子），在体内催化纤维形成过程。
