Molecular-level secondary structure, polymorphism, and dynamics of full-length ¿-synuclein fibrils studied by solid-state NMR

摘要: Abstract The 140-residue protein α-synuclein (AS) is able to form amyloid fibrils and as such the main component of inclusions involved in Parkinson's disease. We have investigated structure dynamics full-length AS by high-resolution solid-state NMR spectroscopy. Homonuclear heteronuclear 2D 3D spectra grown from uniformly 13C/15N-labeled reverse-labeled for two most abundant amino acids, K V, were analyzed. 13C 15N signals exhibited linewidths <0.7 ppm. Sequential assignments obtained 48 residues hydrophobic core region. identified different types displaying chemical-shift differences up 13 ppm dimension 5 backbone side-chain chemical shifts. EM studies suggested that molecular correlated with fibril morphology. Investigation secondary revealed acids region belong β-strands similar torsion angles both conformations. Selection regions mobility indicated existence monomers sample allowed identification mobile segments within presence monomeric protein. At least 35 C-terminal lacked a defined structure, whereas N terminus was rigid starting residue 22. Our findings agree well overall picture other methods provide insight into residue-specific resolution. EM protein structure amyloid Parkinson's disease protein aggregation