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Physical basis of amyloid fibril polymorphism

TitlePhysical basis of amyloid fibril polymorphism
Publication TypeJournal Article
Year of Publication2018
AuthorsClose, W, Neumann M, Schmidt A, Hora M, Annamalai K, Schmidt M, Reif B, Schmidt V, Grigorieff N, Fändrich M
Refereed DesignationRefereed
JournalNature Communications
Date Published12/2018
KeywordsCryoelectron Microscopy, Protein aggregation, self-assembly

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.

Short TitleNat Commun
Close_NatureComm2018.pdf4.57 MB