Binding of zinc(II) and copper(II) to the full-length Alzheimer's amyloid-beta peptide

J Neurochem. 2008 Mar;104(5):1249-59. doi: 10.1111/j.1471-4159.2007.05061.x.


There is evidence that binding of metal ions like Zn2+ and Cu2+ to amyloid beta-peptides (Abeta) may contribute to the pathogenesis of Alzheimer's disease. Cu2+ and Zn2+ form complexes with Abeta peptides in vitro; however, the published metal-binding affinities of Abeta vary in an enormously large range. We studied the interactions of Cu2+ and Zn2+ with monomeric Abeta(40) under different conditions using intrinsic Abeta fluorescence and metal-selective fluorescent dyes. We showed that Cu(2+) forms a stable and soluble 1 : 1 complex with Abeta(40), however, buffer compounds act as competitive copper-binding ligands and affect the apparent K(D). Buffer-independent conditional K(D) for Cu(II)-Abeta(40) complex at pH 7.4 is equal to 0.035 micromol/L. Interaction of Abeta(40) with Zn2+ is more complicated as partial aggregation of the peptide occurs during zinc titration experiment and in the same time period (within 30 min) the initial Zn-Abeta(40) complex (K(D) = 60 micromol/L) undergoes a transition to a more tight complex with K(D) approximately 2 micromol/L. Competition of Abeta(40) with ion-selective fluorescent dyes Phen Green and Zincon showed that the K(D) values determined from intrinsic fluorescence of Abeta correspond to the binding of the first Cu2+ and Zn2+ ions to the peptide with the highest affinity. Interaction of both Zn2+ and Cu2+ ions with Abeta peptides may occur in brain areas affected by Alzheimer's disease and Zn2+-induced transition in the peptide structure might contribute to amyloid plaque formation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Binding, Competitive
  • Brain Chemistry
  • Cations, Divalent / chemistry
  • Cations, Divalent / metabolism
  • Copper / chemistry
  • Copper / metabolism*
  • Dose-Response Relationship, Drug
  • Oxidation-Reduction
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Protein Binding
  • Spectrometry, Fluorescence
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Spectrophotometry, Ultraviolet
  • Zinc / chemistry
  • Zinc / metabolism*


  • Amyloid beta-Peptides
  • Cations, Divalent
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • Copper
  • Zinc