Guo Jun-tao, Wetzel Ronald, Xu Ying
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA.
Proteins. 2004 Nov 1;57(2):357-64. doi: 10.1002/prot.20222.
Amyloid fibrils, a key pathological feature of Alzheimer's disease (AD) and other amyloidosis implicated in neurodegeneration, have a characteristic cross-beta structure. Here we present a structural model for the core of amyloid fibrils formed by the Abeta peptide using computational approaches and experimental data. Abeta(15-36) was threaded against the parallel beta-helical proteins. Our multi-layer model was constructed using the top scoring template 1lxa, a left-handed parallel beta-helical protein. This six-rung helical model has in-register repeats of the Abeta(15-36) sequence. Each rung has three beta-strands separated by two turns. The model was tested using molecular dynamics simulations in explicit water, and is in good agreement with a number of experimental observations. In addition, a model based on right-handed helical proteins is also described. The core structural model described here might serve as the building block of the Abeta(1-40) amyloid fibril as well as some other amyloid fibrils.
淀粉样纤维是阿尔茨海默病（AD）以及其他与神经退行性变相关的淀粉样变性的关键病理特征，具有特征性的交叉β结构。在此，我们利用计算方法和实验数据，提出了一种由β淀粉样肽形成的淀粉样纤维核心的结构模型。β淀粉样蛋白（15 - 36）序列与平行β螺旋蛋白进行比对。我们的多层模型是使用得分最高的模板1lxa构建的，1lxa是一种左手平行β螺旋蛋白。这个六环螺旋模型具有β淀粉样蛋白（15 - 36）序列的对齐重复。每个环有三条由两圈隔开的β链。该模型在明确的水环境中通过分子动力学模拟进行了测试，并且与许多实验观察结果高度吻合。此外，还描述了一种基于右手螺旋蛋白的模型。这里描述的核心结构模型可能是β淀粉样蛋白（1 - 40）淀粉样纤维以及其他一些淀粉样纤维的构建模块。
