title: Citrullination and deamidation affect aggregation properties of amyloid β-proteins.
abstract: Citrullination and deamidation, which are aging-related posttranslational modifications, increase the number of negative charges on amyloid β-protein (Aβ) at neutral pH. We investigated the effects of these modifications on the fibrillation properties of Aβ. The Arg5→Cit modification of Aβ1-40did not affect the fibrillation rate, and brought β-sheet structures unlike that in the Aβ1-40fibril. The Asn27→Asp modification of Aβ1-40stopped the fibrillation and induced the formation of aggregates that involved an anti-parallel β-sheet. Aβ1-42with the Arg5→Cit modification showed increased solubility in aqueous media, and its fibril formation became slower than that of Aβ1-42. The modification did not change the parallel β-sheet structure of the fibrils. Aβ1-42with the Asn27→Asp modification partially formed fibrils that involved the parallel β-sheet structure. Using the thioflavin T (ThT) assay, an increased fraction of the soluble oligomer of each Aβ analog was transiently detected during fibrillation. An increase in the number of negative charges at basic pH affected the aggregation properties of Aβ in a manner different from that with the modifications, suggesting that change in properties of the posttanslationally modified residues rather than the number of charges in the peptide was important.
authors: a Graduate School of Pharmaceutical Sciences, Tohoku University , Sendai , Japan.
authors: Dai
authors: D
authors: Osaki
authors: a Graduate School of Pharmaceutical Sciences, Tohoku University , Sendai , Japan.
authors: Hirotsugu
authors: H
authors: Hiramatsu
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D052160:Benzothiazoles; D002956:Citrulline / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates; D000072757:Protein Conformation, beta-Strand; D011499:Protein Processing, Post-Translational; D012995:Solubility; D055672:Static Electricity; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000577:Amides; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D010446:Peptide Fragments; D066329:Protein Aggregates; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C009462:thioflavin T; D002956:Citrulline
keywords: Charge; oligomer; pH dependence; salt bridge; secondary structure