title: Polymorphism of fibrillar structures depending on the size of assembled Aβ17-42peptides.
abstract: The size of assembled Aβ17-42peptides can determine polymorphism during oligomerization and fibrillization, but the mechanism of this effect is unknown. Starting from separate random monomers, various fibrillar oligomers with distinct structural characteristics were identified using discontinuous molecular dynamics simulations based on a coarse-grained protein model. From the structures observed in the simulations, two characteristic oligomer sizes emerged, trimer and paranuclei, which generated distinct structural patterns during fibrillization. A majority of the simulations for trimers and tetramers formed non-fibrillar oligomers, which primarily progress to off-pathway oligomers. Pentamers and hexamers were significantly converted into U-shape fibrillar structures, meaning that these oligomers, called paranuclei, might be potent on-pathway intermediates in fibril formation. Fibrillar oligomers larger than hexamers generated substantial polymorphism in which hybrid structures were readily formed and homogeneous fibrillar structures appeared infrequently.
authors.affiliation: Center for Proteome Biophysics, Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.|Department of Neural Development and Disease, Korea Brain Research Institute, Daegu 41068, Korea.
authors.forename: Mookyung
authors.initials: M
authors.lastname: Cheon
authors.affiliation: Center for Proteome Biophysics, Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.
authors.forename: Mooseok
authors.initials: M
authors.lastname: Kang
authors.affiliation: Center for Proteome Biophysics, Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.
authors.forename: Iksoo
authors.initials: I
authors.lastname: Chang
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C086839:amyloid beta-protein (17-42)