Losic Dusan, Martin Lisandra L, Mechler Adam, Aguilar Marie-Isabel, Small David H
Department of Biochemistry and Molecular Biology, Monash University, Vic. 3800, Australia.
J Struct Biol. 2006 Jul;155(1):104-10. doi: 10.1016/j.jsb.2006.02.013. Epub 2006 Mar 31.
The aggregation of the beta-amyloid protein (Abeta) is an important step in the pathogenesis of Alzheimer's disease. There is increasing evidence that lower molecular weight oligomeric forms of Abeta may be the most toxic species in vivo. However, little is known about the structure of Abeta oligomers. In this study, scanning tunnelling microscopy (STM) was used to examine the structure of Abeta monomers, dimers and oligomers. Abeta1-40 was visualised by STM on a surface of atomically flat gold. At low concentrations (0.5 microM) small globular structures were observed. High resolution STM of these structures revealed them to be monomers of Abeta. The monomers measured approximately 3-4 nm in diameter. Internal structure was seen in many of the monomers consistent with a conformation in which the polypeptide chain is folded into 3 or 4 domains. Oligomers were seen after ageing the Abeta solution for 24 h. The oligomers were also 3-4 nm in width and appeared to be formed by the end-to-end association of monomers with the polypeptide chain oriented at 90 degrees to the axis of the oligomer. The results suggest that the oligomer formation can proceed through a mechanism involving the linear association of monomers.
β-淀粉样蛋白（Aβ）的聚集是阿尔茨海默病发病机制中的一个重要步骤。越来越多的证据表明，低分子量的Aβ寡聚体形式可能是体内毒性最强的物质。然而，人们对Aβ寡聚体的结构知之甚少。在本研究中，扫描隧道显微镜（STM）被用于检测Aβ单体、二聚体和寡聚体的结构。Aβ1-40在原子级平整的金表面上通过STM成像。在低浓度（0.5微摩尔）下观察到小球状结构。这些结构的高分辨率STM显示它们是Aβ单体。单体直径约为3-4纳米。在许多单体中观察到内部结构，这与多肽链折叠成3或4个结构域的构象一致。在Aβ溶液老化24小时后观察到寡聚体。寡聚体宽度也为3-4纳米，似乎是由单体的端对端缔合形成的，多肽链与寡聚体轴呈90度取向。结果表明，寡聚体的形成可以通过涉及单体线性缔合的机制进行。
