title: Effect of the Tottori familial disease mutation (D7N) on the monomers and dimers of Aβ40 and Aβ42.
abstract: Recent experiments have shown that the mutation Tottori (D7N) alters the toxicity, assembly and rate of fibril formation of the wild type (WT) amyloid beta (Aβ) Aβ40 and Aβ42 peptides. We used all-atom molecular dynamics simulations in explicit solvent of the monomer and dimer of both alloforms with their WT and D7N sequences. The monomer simulations starting from a random coil and totaling 3 μs show that the D7N mutation changes the fold and the network of salt bridges in both alloforms. The dimer simulations starting from the amyloid fibrillar states and totaling 4.4 μs also reveal noticeable changes in terms of secondary structure, salt bridge, and topology. Overall, this study provides physical insights into the enhanced rate of fibril formation upon D7N mutation and an atomic picture of the D7N-mediated conformational change on Aβ40 and Aβ42 peptides.
authors.affiliation: Institute of Physics, Polish Academy of Sciences , Al. Lotnikow 32/46, 02-668 Warsaw, Poland.
authors.forename: Man Hoang
authors.initials: MH
authors.lastname: Viet
authors.forename: Phuong H
authors.initials: PH
authors.lastname: Nguyen
authors.forename: Son Tung
authors.initials: ST
authors.lastname: Ngo
authors.forename: Mai Suan
authors.initials: MS
authors.lastname: Li
authors.forename: Philippe
authors.initials: P
authors.lastname: Derreumaux
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000586:Amination; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000235:genetics; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D055503:Protein Multimerization / Q000235:genetics; D017433:Protein Structure, Secondary / Q000235:genetics; D055672:Static Electricity; D013379:Substrate Specificity / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D046912:Multiprotein Complexes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C538897:amyloid beta-protein (40-42); D001224:Aspartic Acid; D001216:Asparagine; D008239:Lysine
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