Copper selectively triggers β-sheet assembly of an N-terminally truncated amyloid β-peptide beginning with Glu3

Takashi Miura, Sayoko Mitani, Chiho Takanashi, Nobuhiro Mochizuki

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Metal ions have been suggested to induce aggregation of amyloid β-peptide (Aβ), which is a key event in Alzheimer's disease. However, direct evidence that specific metal-peptide interactions are responsible for the amyloid formation has not previously been provided. Here we present the first example of the metal-induced amyloid formation by an Aβ fragment, which exhibits a clear-cut dependence on the amino acid sequence. A heptapeptide, EFRHDSG, corresponding to the amino acid residues 3-9 of Aβ (Aβ3-9) undergoes a conformational transition from irregular to β-sheet and self-associates into insoluble aggregates upon Cu(II) binding. A Raman spectrum analysis of the Cu(II)-Aβ3-9 complex and aggregation assays of mutated Aβ3-9 peptides demonstrated that a concerted Cu(II) coordination of the imidazole side chain of His6, the carboxyl groups of Glu3 and Asp7, and the amino group at the N-terminus is essential for the amyloid formation. Although Aβ1-9 and Aβ2-9 also contain the metal binding sites, neither of these peptides forms amyloid depositions in the presence of Cu(II). The results of this study may not only provide new insight into the mechanism of amyloid formation, but also be important as a step toward the construction of proteinaceous materials with a specific function under the control of Cu(II).

Original languageEnglish
Pages (from-to)10-14
Number of pages5
JournalJournal of Inorganic Biochemistry
Volume98
Issue number1
DOIs
Publication statusPublished - 2004 Jan 1

Keywords

  • Amyloid β-peptide
  • Copper
  • Raman spectroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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