Nonfibrous β-structured aggregation of an Aβ model peptide (Ad-2α) on GM1/DPPC mixed monolayer surfaces
Nonfibrous β-structured aggregation of an Aβ model peptide (Ad-2α) on GM1/DPPC mixed monolayer surfaces
复制标题
DOI：
10.1016/j.jcis.2005.07.027
复制
发表时间：
2006-02-15
影响因子：
9.9
通讯作者：
Okahata, Y
中科院分区：
文献类型：
--
作者：
Kawasaki, T;Asaoka, K;Okahata, Y
转化的肽和蛋白质在细胞膜表面上的吸附和聚集通常与淀粉样变性的形式如阿尔茨海默病和朊病毒病有关。为了解决这些病理现象的分子动力学特征，原位Ad-2 α模型肽沉积糖脂含单分子膜上进行了研究，通过使用9 MHz的石英晶体微天平（QCM）。Ad-2a肽具有两个两亲性α-螺旋片段，每个片段在N-末端用1-金刚烷羰基修饰作为疏水缺陷。肽在本体溶液中以2 α-螺旋结构折叠。在存在层压在QCM板上的糖脂（GM 1、去唾液酸-GM 1、GM 3或LacCer）和/或二棕榈酰磷脂酰胆碱（DPPC）的混合单层的情况下，肽沉积和单层上的β-结构的构象变化被加速。吸附动力学和Ad-2 α的量依赖于DPPC基质中糖脂的种类和含量。尽管Ad-2a肽以单层覆盖的形式吸附在大多数糖脂膜上，但它主要吸附在GM 1/DPPC（30/70摩尔%）混合单层上，具有特征动力学行为。通过AFM和荧光显微镜用硫磺素T（ThT）证实了β-结构非纤维聚集体的形成。(c)2005年爱思唯尔公司All rights reserved.
Adsorption and aggregation of transformed peptides and proteins onto the cell membrane surface is commonly associated with forms of amyloidosis such as Alzheimer's disease and prion disease. To address dynamic features of these pathological phenomena molecularly, the in situ Ad-2 alpha model peptide deposition on glycolipid-containing monolayers was studied by using a 9 MHz quartz-crystal microbalance (QCM). The Ad-2a peptide has two amphiphilic alpha-helix segments, each modified with a 1-adamantanecarbonyl group at the N-terminal as a hydrophobic defect. The peptide folds in a 2 alpha-helix structure in the bulk solution. In the presence of mixed monolayers of glycolipids (GM 1, asialo-GM 1, GM3, or LacCer) and/or dipalmitoyl phosphatidylcholine (DPPC) laminated on the QCM plate, the peptide deposition and the conformational change to beta-structure on the monolayers were accelerated. The adsorption kinetics and the amount of Ad-2 alpha were dependent on the sort and contents of the glycolipid in the DPPC matrix. Although the Ad-2a peptide adsorbs onto most of the glycolipid membranes as monolayer coverage, it adsorbed largely onto the GM1/DPPC (30/70 mol%) mixed monolayer with characteristic kinetic behaviors. The accurnulation of beta-structured nonfibrous aggregations was confirmed by AFM and fluorescence microscopy with Thioflavin T (ThT). (c) 2005 Elsevier Inc. All rights reserved.