RESUMO
The amyloid fibrils of beta-amyloid (Aß) peptides play important roles in the pathology of Alzheimer's disease. Comprehensive solid-state NMR (SSNMR) structural studies on uniformly isotope-labeled Aß 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 Aß(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-ß-strand contacts within the U-shaped ß-strand-turn-ß-strand motif are shifted, the N-terminal region adopts a ß-conformation, and new inter-monomer contacts occur at the protofilament interface. The revealed structural diversity in Aß fibrils points to a complex picture of Aß fibrillation.
