Interactions of amyloid β-peptide (1-40) with ganglioside-containing membranes
Interactions of amyloid β-peptide (1-40) with ganglioside-containing membranes
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DOI：
10.1021/bi982345o
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发表时间：
1999-03-30
期刊：
影响因子：
2.9
通讯作者：
Horikiri, C
中科院分区：
文献类型：
--
作者：
Matsuzaki, K;Horikiri, C
淀粉样β-肽（A β）和神经元膜之间的相互作用已被假定在阿尔茨海默病的神经病理学中发挥重要作用。为了深入了解这种关联的分子细节，我们通过圆二色性（CD）和傅里叶变换红外偏振衰减全反射（FTIR-PATR）光谱研究了A β（1-40）与含有神经节苷脂的膜的相互作用。CD研究显示，在生理离子强度下，A β（1-40）特异性结合含有神经节苷脂的膜，诱导高于阈值膜内神经节苷脂浓度的两种状态的无序β-折叠转变，这取决于所使用的宿主脂质双层。此外，糖骨架的唾液酸残基的数量和位置的差异显着影响肽的构象转变。FTIR-PATR光谱实验表明，A β（1-40）形成一个反平行的β-折叠，其平面平行于膜表面，诱导脂质界面基团的脱水和酰基链取向的扰动。这些结果表明，A β（1-40）对含有神经节苷脂的脂质双层施加负曲率应变，干扰膜的结构和功能。
Interactions between amyloid beta-peptides (A beta) and neuronal membranes have been postulated to play an important role in the neuropathology of Alzheimer's disease. To gain insight into the molecular details of this association, we investigated the interactions of A beta (1-40) with ganglioside-containing membranes by circular dichroism (CD) and Fourier transform infrared-polarized attenuated total reflection (FTIR-PATR) spectroscopy. The CD study revealed that at physiological ionic strength A beta (1-40) specifically binds to ganglioside-containing membranes inducing a two-state, unordered --> beta-sheet transition above a threshold intramembrane ganglioside concentration, which depends on the host lipid bilayers used. Furthermore, differences in the number and position of sialic acid residues of the carbohydrate backbone significantly affected the conformational transition of the peptide. FTIR-PATR spectroscopy experiments demonstrated that A beta (1-40) forms an antiparallel beta-sheet, the plane of which lies parallel to the membrane surface, inducing dehydration of lipid interfacial groups and perturbation of acyl chain orientation. These results suggest that A beta (1-40) imposes negative curvature strain on ganglioside-containing lipid bilayers, disturbing the structure and function of the membranes.