Journal of the American Chemical Society · 2011 · 309 citations · 83 references
Life SciencesBiochemistryMolecular BiologyNeurodegenerationStructural BiochemistryStructural BiologyAlzheimer DiseaseAmyloid FormationMacromolecular AssemblyMacromolecular StructureNeurodegenerative DiseasesProtein ConformationAmyloid Beta AggregationAmyloid Beta PeptidesAmyloid Fibril FormationAmyloid Fibril StructureAmyloid FibrillogenesisAmyloid FibrilsAmyloid StructureN-terminal Region Structure
The amyloid fibrils of beta-amyloid (Aβ) peptides play important roles in the pathology of Alzheimer's disease. Comprehensive solid-state NMR (SSNMR) structural studies on uniformly isotope-labeled Aβ assemblies have been hampered for a long time by sample heterogeneity and low spectral resolution. In this work, SSNMR studies on well-ordered fibril samples of Aβ(40) with an additional N-terminal methionine provide high-resolution spectra which lead to an accurate structural model. The fibrils studied here carry distinct structural features compared to previous reports. The inter-β-strand contacts within the U-shaped β-strand-turn-β-strand motif are shifted, the N-terminal region adopts a β-conformation, and new inter-monomer contacts occur at the protofilament interface. The revealed structural diversity in Aβ fibrils points to a complex picture of Aβ fibrillation.
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Atomic structures of amyloid cross-β spines reveal varied steric zippers
M.R. Sawaya, Shilpa Sambashivan, Rebecca A. Nelson et al. · Nature · 2007 · 2.3K citations