Citrullination and deamidation affect aggregation properties of amyloid β-proteins

Dai Osaki, Hirotsugu Hiramatsu

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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 Aβ1–40 did not affect the fibrillation rate, and brought β-sheet structures unlike that in the Aβ1–40 fibril. The Asn27→Asp modification of Aβ1–40 stopped the fibrillation and induced the formation of aggregates that involved an anti-parallel β-sheet. Aβ1–42 with 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. Aβ1–42 with 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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalAmyloid
DOIs
Publication statusAccepted/In press - 2016 Mar 28

Keywords

  • Charge
  • oligomer
  • pH dependence
  • salt bridge
  • secondary structure

ASJC Scopus subject areas

  • Internal Medicine

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