Institute of Protein Biochemistry, Ulm University, 89081, Ulm, Germany.
Institute of Stochastics, Ulm University, 89081, Ulm, Germany.
Nat Commun. 2018 Feb 16;9(1):699. doi: 10.1038/s41467-018-03164-5.
Polymorphism is a key feature of amyloid fibril structures but it remains challenging to explain these variations for a particular sample. Here, we report electron cryomicroscopy-based reconstructions from different fibril morphologies formed by a peptide fragment from an amyloidogenic immunoglobulin light chain. The observed fibril morphologies vary in the number and cross-sectional arrangement of a structurally conserved building block. A comparison with the theoretically possible constellations reveals the experimentally observed spectrum of fibril morphologies to be governed by opposing sets of forces that primarily arise from the β-sheet twist, as well as peptide-peptide interactions within the fibril cross-section. Our results provide a framework for rationalizing and predicting the structure and polymorphism of cross-β fibrils, and suggest that a small number of physical parameters control the observed fibril architectures.
多态性是淀粉样纤维结构的一个关键特征，但要解释特定样品中的这些变化仍然具有挑战性。在这里，我们报告了由免疫球蛋白轻链的肽片段形成的不同纤维形态的基于电子 cryomicroscopy 的重建。观察到的纤维形态在结构保守构建块的数量和横截面排列上有所不同。与理论上可能的组合进行比较表明，实验观察到的纤维形态谱受主要来自β-折叠扭曲以及纤维横截面内肽-肽相互作用的相反力组的控制。我们的结果为合理化和预测交叉-β纤维的结构和多态性提供了一个框架，并表明少量物理参数控制观察到的纤维结构。
