Lau Tong-Lay, Gehman John D, Wade John D, Perez Keyla, Masters Colin L, Barnham Kevin J, Separovic Frances
School of Chemistry, Bio21 Institute, The University of Melbourne, VIC 3010, Australia.
Biochim Biophys Acta. 2007 Oct;1768(10):2400-8. doi: 10.1016/j.bbamem.2007.05.004. Epub 2007 May 22.
Abeta(1-42) peptide, found as aggregated species in Alzheimer's disease brain, is linked to the onset of Alzheimer's disease. Many reports have linked metals to inducing Abeta aggregation and amyloid plaque formation. Abeta(25-35), a fragment from the C-terminal end of Abeta(1-42), lacks the metal coordinating sites found in the full-length peptide and is neurotoxic to cortical cortex cell cultures. We report solid-state NMR studies of Abeta(25-35) in model lipid membrane systems of anionic phospholipids and cholesterol, and compare structural changes to those of Abeta(1-42). When added after vesicle formation, Abeta(25-35) was found to interact with the lipid headgroups and slightly perturb the lipid acyl-chain region; when Abeta(25-35) was included during vesicle formation, it inserted deeper into the bilayer. While Abeta(25-35) retained the same beta-sheet structure irrespective of the mode of addition, the longer Abeta(1-42) appeared to have an increase in beta-sheet structure at the C-terminus when added to phospholipid liposomes after vesicle formation. Since the Abeta(25-35) fragment is also neurotoxic, the full-length peptide may have more than one pathway for toxicity.
在阿尔茨海默病大脑中以聚集形式存在的β-淀粉样蛋白（1-42）肽与阿尔茨海默病的发病有关。许多报告将金属与诱导β-淀粉样蛋白聚集和淀粉样斑块形成联系起来。β-淀粉样蛋白（25-35）是β-淀粉样蛋白（1-42）C末端的一个片段，缺乏全长肽中发现的金属配位位点，对皮质细胞培养物具有神经毒性。我们报告了在阴离子磷脂和胆固醇的模型脂质膜系统中对β-淀粉样蛋白（25-35）的固态核磁共振研究，并将结构变化与β-淀粉样蛋白（1-42）的结构变化进行了比较。在囊泡形成后添加时，发现β-淀粉样蛋白（25-35）与脂质头部基团相互作用，并轻微扰动脂质酰链区域；当在囊泡形成过程中加入β-淀粉样蛋白（25-35）时，它会更深地插入双层膜中。虽然无论添加方式如何，β-淀粉样蛋白（25-35）都保持相同的β-折叠结构，但在囊泡形成后添加到磷脂脂质体中时，较长的β-淀粉样蛋白（1-42）在C末端的β-折叠结构似乎有所增加。由于β-淀粉样蛋白（25-35）片段也具有神经毒性，全长肽可能有不止一条毒性途径。
