The protofilament structure of insulin amyloid fibrils
The protofilament structure of insulin amyloid fibrils
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DOI：
10.1073/pnas.142459399
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发表时间：
2002-07-09
影响因子：
11.1
通讯作者：
Saibil, HR
中科院分区：
文献类型：
--
作者：
Jimenez, JL;Nettleton, EJ;Saibil, HR
在天然状态不稳定的溶液条件下，大部分螺旋多肽激素胰岛素容易聚集形成具有特征性交叉β结构的淀粉样蛋白原纤维。然而，缺乏关于4.8埃β链重复与淀粉样蛋白原纤维的更高级组装的信息。我们已经使用冷冻电子显微镜（EM），结合单颗粒分析和螺旋重建，这些原纤维的特点，并研究其组成原丝的三维（3D）排列。含有2、4和6个原丝的原纤维的低分辨率3D结构揭示了胰岛素原丝的特征性紧凑形状。原丝包装的考虑表明，交叉β带是由相对平坦的β-片层，而不是高度扭曲，β-螺旋结构先前建议通过分析球状蛋白质折叠。各种原纤维结构的比较表明，非常小的，β-片层扭曲的局部变化是重要的，在建立远程卷曲的原丝成原纤维的不同形态。
Under solution conditions where the native state is destabilized, the largely helical polypeptide hormone insulin readily aggregates to form amyloid fibrils with a characteristic cross-beta structure. However, there is a lack of information relating the 4.8 Angstrom beta-strand repeat to the higher order assembly of amyloid fibrils. We have used cryo-electron microscopy (EM), combining single particle analysis and helical reconstruction, to characterize these fibrils and to study the three-dimensional (3D) arrangement of their component protofilaments. Low-resolution 3D structures of fibrils containing 2, 4, and 6 protofilaments reveal a characteristic, compact shape of the insulin protofilament. Considerations of protofilament packing indicate that the cross-beta ribbon is composed of relatively flat beta-sheets rather than being the highly twisted, beta-coil structure previously suggested by analysis of globular protein folds. Comparison of the various fibril structures suggests that very small, local changes in beta-sheet twist are important in establishing the long-range coiling of the protofilaments into fibrils of diverse morphology.