The Common Architecture of Cross-β Amyloid
The Common Architecture of Cross-β Amyloid
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DOI：
10.1016/j.jmb.2009.09.039
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发表时间：
2010-01-29
影响因子：
5.6
通讯作者：
Serpell, Louise C.
中科院分区：
文献类型：
--
作者：
Jahn, Thomas R.;Makin, O. Sumner;Serpell, Louise C.
淀粉样蛋白纤维沉积是30多种不相关疾病的核心病理，包括阿尔茨海默病和2型糖尿病。人们普遍认为淀粉样蛋白原纤维具有共同的结构特征，尽管每种疾病都以不相关蛋白或肽的沉积为特征。淀粉样蛋白原纤维的结构已经用x射线纤维衍射和晶体学、固体核磁共振和电子顺磁共振进行了研究，并提出了许多不同的，有时是相反的模型。这些模型中的许多都是基于对交叉- β丝的交叉- β衍射模式的原始解释，其中- β链垂直于纤维轴，尽管其他模型包括p-螺旋和天然结构蛋白质。在这里，我们分析了相反的模型结构，检查了淀粉样蛋白核心结构中必要的结构元素，并产生了理想的模型来测试核心构象的极限。我们的工作支持淀粉样蛋白原纤维具有许多共同的结构特征，从而产生特征衍射图案的观点。这种模式可以通过这样的结构来满足，在这种结构中，链排列接近于垂直于纤维轴，并有规则地排列成β片带。此外，原丝结构包含几个β片，它们通过侧链包装结合形成最终的原丝结构。2009爱思唯尔有限公司版权所有。
Amyloid fibril deposition is central to the pathology of more than 30 unrelated diseases including Alzheimer's disease and Type 2 diabetes. It is generally accepted that amyloid fibrils share common structural features despite each disease being characterised by the deposition of an unrelated protein or peptide. The structure of amyloid fibrils has been studied using X-ray fibre diffraction and crystallography, solid-state NMR and electron paramagnetic resonance, and many different, sometimes opposing, models have been suggested. Many of these models are based on the original interpretation of the cross-beta diffraction pattern for cross-beta silk in which beta-strands run perpendicular to the fibre axis, although alternative models include p-helices and natively structured proteins. Here, we have analysed opposing model structures and examined the necessary structural elements within the amyloid core structure, as well as producing idealised models to test the limits of the core conformation. Our work supports the view that amyloid fibrils share a number of common structural features, resulting in characteristic diffraction patterns. This pattern may be satisfied by structures in which the strands align close to perpendicular to the fibre axis and are regularly arranged to form beta-sheet ribbons. Furthermore, the fibril structure contains several beta-sheets that associate via side-chain packing to form the final protofilament structure. (C) 2009 Elsevier Ltd. All rights reserved.