title: Structure and aggregation mechanism of beta(2)-microglobulin (83-99) peptides studied by molecular dynamics simulations.
abstract: Many human neurodegenerative diseases are associated with amyloid fibril formation. The human 99-residue beta(2)-microglobulin (beta2m) is one of the most intensively studied amyloid-forming proteins. Recent studies show that the C-terminal fragments 72-99, 83-89, and 91-96 form by themselves amyloid fibrils in vitro and play a significant role in fibrillization of the full-length beta2m protein under acidic pH conditions. In this work, we have studied the equilibrium structures of the 17-residue fragment 83-99 in solution, and investigated its dimerization process by multiple molecular dynamics simulations. We find that an intertwined dimer, with the positions of the beta-strands consistent with the results for the monomer, is a possible structure for two beta2m(83-89) peptides. Based on our molecular-dynamics-generated dimeric structure, a protofibril model is proposed for the full-length beta2m protein.
authors: National Key Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai, China.
authors: Chungwen
authors: C
authors: Liang
authors: Philippe
authors: P
authors: Derreumaux
authors: Guanghong
authors: G
authors: Wei
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry; D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D019281:Dimerization; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D001613:beta 2-Microglobulin / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides; D001613:beta 2-Microglobulin
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