Molecular mechanism of the self-propagation of amyloid fibrils explored by structural analysis of prefibrillar intermediates

蛋白质的错误折叠有时会导致被称为淀粉样纤维的超分子组合体的形成，其沉积与许多疾病有关。淀粉样蛋白纤维最独特和最基本的特性之一是其依赖于模板的生长，这是淀粉样变性病理传播的基础。在这项研究中，我们捕获了在纤颤反应早期瞬间形成的胰岛素的前纤维中间体，并通过AFM、FTIR和蛋白水解酶分析了详细的结构特性，已证明有几个区域对淀粉样蛋白的繁殖是必不可少的。

Protein misfolding occasionally leads to the formation of supramolecular assemblies known as amyloid fibrils, the deposition of which is associated with numerous diseases. One of the most unique and essential properties of amyloid fibrils is their template-dependent growth, which underlies the propagation of pathology of amyloidoses. In this study, we trapped a prefibrillar intermediate of insulin formed transiently in the early stage of fibrillation reaction and from detailed structural properties analyzed by using AFM, FTIR, and proteolytic digestion, several regions have proved to be essential for the amyloid propagation