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

作者：Tougu Vello^*; Karafin Ann; Palumaa Peep

来源：Journal of Neurochemistry, 2008, 104(5): 1249-1259.

DOI：10.1111/j.1471-4159.2007.05061.x

• Alzheimer's disease
• amyloid-beta peptide
• binding constants
• copper
• zinc

There is evidence that binding of metal ions like Zn2+ and Cu2+ to amyloid beta-peptides (A beta) may contribute to the pathogenesis of Alzheimer's disease. Cu2+ and Zn2+ form complexes with Ab peptides in vitro; however, the published metal-binding affinities of Ab vary in an enormously large range. We studied the interactions of Cu2+ and Zn2+ with monomeric A beta(40) under different conditions using intrinsic Ab fluorescence and metal-selective fluorescent dyes. We showed that Cu2+ forms a stable and soluble 1:1 complex with Ab40, however, buffer compounds act as competitive copper-binding ligands and affect the apparent K-D. Buffer-independent conditional K-D for Cu(II)-A beta(40) complex at pH 7.4 is equal to 0.035 mu mol/L. Interaction of A beta(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-A beta(40) complex (K-D = 60 mu mol/L) undergoes a transition to a more tight complex with K-D similar to 2 mu mol/L Competition of A beta(40) with ion-selective fluorescent dyes Phen Green and Zincon showed that the KD values determined from intrinsic fluorescence of Ab 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 Ab 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.

• 出版日期2008-3