Wetzel Ronald, Shivaprasad Shankaramma, Williams Angela D
Graduate School of Medicine, University of Tennessee, Knoxville Tennessee 37920, USA.
Biochemistry. 2007 Jan 9;46(1):1-10. doi: 10.1021/bi0620959.
In experiments designed to characterize the basis of amyloid fibril stability through mutational analysis of the Abeta (1-40) molecule, fibrils exhibit consistent, significant structural malleability. In these results, and in other properties, amyloid fibrils appear to more resemble plastic materials generated from synthetic polymers than globular proteins. Thus, like synthetic polymers and plastics, amyloid fibrils exhibit both polymorphism, the ability of one polypeptide to form aggregates of different morphologies, and isomorphism, the ability of different polypeptides to grow into a fibrillar amyloid morphology. This view links amyloid with the prehistorical and 20th century use of proteins as starting materials to make films, fibers, and plastics, and with the classic protein fiber stretching experiments of the Astbury group. Viewing amyloids from the point of view of the polymer chemist may shed new light on a number of issues, such as the role of protofibrils in the mechanism of amyloid formation, the biological potency of fibrils, and the prospects for discovering inhibitors of amyloid fibril formation.
在旨在通过对β淀粉样蛋白（1-40）分子进行突变分析来表征淀粉样纤维稳定性基础的实验中，纤维表现出一致且显著的结构可塑性。从这些结果以及其他特性来看，淀粉样纤维似乎更类似于由合成聚合物生成的塑性材料，而非球状蛋白质。因此，与合成聚合物和塑料一样，淀粉样纤维既表现出多态性，即一种多肽形成不同形态聚集体的能力，也表现出同构性，即不同多肽生长成纤维状淀粉样形态的能力。这种观点将淀粉样蛋白与蛋白质在史前及20世纪作为制造薄膜、纤维和塑料的起始材料的用途联系起来，也与阿斯特伯里团队经典的蛋白质纤维拉伸实验相关。从聚合物化学家的角度看待淀粉样蛋白可能会为诸多问题带来新的启示，比如原纤维在淀粉样蛋白形成机制中的作用、纤维的生物活性以及发现淀粉样纤维形成抑制剂的前景。
