Physical basis of amyloid fibril polymorphism.

ABSTRACT: 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 ?-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-? fibrils, and suggest that a small number of physical parameters control the observed fibril architectures.

SUBMITTER: Close W 

PROVIDER: S-EPMC5816019 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature