DHPC Strongly Affects the Structure and Oligomerization Propensity of Alzheimer's Aβ(1-40) Peptide
DHPC Strongly Affects the Structure and Oligomerization Propensity of Alzheimer's Aβ(1-40) Peptide
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DOI：
10.1016/j.jmb.2010.09.021
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发表时间：
2010-11-05
影响因子：
5.6
通讯作者：
Fahr, Alfred
中科院分区：
文献类型：
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作者：
Dahse, Kirsten;Garvey, Megan;Fahr, Alfred
阿尔茨海默病（AD）被认为依赖于淀粉样蛋白原纤维或β -淀粉样蛋白（A β）肽衍生的低聚物的有害作用。在各种已知的A β同种异体中，40-残基肽A β(1-40)在AD患者的大脑中浓度最高。它的聚集特性严重依赖于脂质，因此提出脂质可能在AD中起主要作用。为了更好地了解它们对A β结构的可能影响，以及对这种肽形成潜在有害淀粉样蛋白结构的能力的影响，我们在这里分析了A β(1-40)和1,2-二己醇-锡-甘油-3-磷酸胆碱（DHPC）之间的相互作用。DHPC由于其可控制的性质，已成为研究一般脂质性质的主要模型体系。在这里，我们发现8 mM或更高浓度的DHPC对可溶性A β(1-40)肽的构象产生显著影响，并诱导高水平β -片结构的形成。相比之下，我们发现远低于临界胶束浓度的DHPC浓度对可溶性A β的构象没有明显的影响，尽管它们实质上影响肽的寡聚化和纤颤动力学。这些数据表明，微妙的脂肽相互作用足以控制总体聚集特性，并大大加速或延迟A -肽在接近生理缓冲溶液中的纤颤动力学。(C) 2010 Elsevier Ltd.版权所有。
Alzheimer's disease (AD) is thought to depend on the deleterious action of amyloid fibrils or oligomers derived from beta-amyloid (A beta) peptide. Out of various known A beta alloforms, the 40-residue peptide A beta(1-40) occurs at highest concentrations inside the brains of AD patients. Its aggregation properties critically depend on lipids, and it was thus proposed that lipids could play a major role in AD. To better understand their possible effects on the structure of A beta and on the ability of this peptide to form potentially detrimental amyloid structures, we here analyze the interactions between A beta(1-40) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). DHPC has served, due to its controlled properties, as a major model system for studying general lipid properties. Here, we show that DHPC concentrations of 8 mM or higher exert dramatic effects on the conformation of soluble A beta(1-40) peptide and induce the formation of beta-sheet structure at high levels. By contrast, we find that DHPC concentrations well below the critical micelle concentration present no discernible effect on the conformation of soluble A beta although they substantially affect the peptide's oligomerization and fibrillation kinetics. These data imply that subtle lipid-peptide interactions suffice in controlling the overall aggregation properties and drastically accelerate, or delay, the fibrillation kinetics of A beta peptide in near-physiological buffer solutions. (C) 2010 Elsevier Ltd. All rights reserved.