Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril

Significance Previous studies suggested that the interactions within amyloid fibrils correspond to those seen in peptide microcrystals consisting of steric zippers. Using electron cryomicroscopy, we can now provide further evidence for this hypothesis in a fibril structure that consists of peptide dimers forming steric zippers. These zippers are arranged in a periodic fibrillar lattice, similar to the periodic structure of a crystal. The fibril structure can be rationalized as a hierarchical assembly that is based on simple chemical principles. Identifying the chemical principles that drive fibril formation may deepen our understanding of human diseases linked to these fibrils and of functional amyloids underlying vital biological functions. Furthermore, it may enable novel biotechnological applications and the design of new fibril-based nanomaterials.