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

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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