Open AccessAmyloid β 42 fibril structure based on small-angle scattering
Author(s) -
Veronica Lattanzi,
Ingemar André,
Urs Gasser,
Marija Dubackic,
Ulf Olsson,
Sara Linse
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2112783118
Subject(s) - fibril , protein filament , monomer , crystallography , chemistry , scattering , peptide , biophysics , fiber diffraction , amyloid (mycology) , protein structure , amyloid fibril , dispersity , small angle scattering , chemical physics , amyloid β , polymer , biochemistry , x ray crystallography , physics , optics , organic chemistry , biology , medicine , inorganic chemistry , disease , pathology , diffraction
Significance Alzheimeŕs disease is one of the major global health challenges. Neuronal cell dysfunction and death are connected to the self-assembly of the amyloid β peptide (Aβ42) into oligomeric and fibrillar aggregates. The fibril surface can catalyze the formation of toxic oligomers via secondary nucleation. Access to a high-resolution structure of Aβ42 fibrils would provide a valuable basis for design of inhibitors of oligomer generation and toxicity in the form of fibril-binders and thus significantly contribute to the development of therapeutics against Alzheimer’s disease. A combination of methods may be most fruitful toward this aim. We show that small-angle X-ray scattering data, in combination with a solid-state NMR structure of the filament core, can reveal a detailed fibril model.