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- Title
Physical basis of amyloid fibril polymorphism.
- Authors
Close, William; Neumann, Matthias; Schmidt, Andreas; Hora, Manuel; Annamalai, Karthikeyan; Schmidt, Matthias; Reif, Bernd; Schmidt, Volker; Grigorieff, Nikolaus; Fändrich, Marcus
- 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 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.
- Subjects
AMYLOID beta-protein
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-03164-5