Interaction of beta-amyloid(1-40) peptide with pairs of metal ions: An electrospray ion trap mass spectrometric model study.
The stoichiometries and the affinity toward simple and paired metal ions of synthetic amyloid-beta(1-40) peptide (Abeta1-40) were investigated by electrospray ion trap mass spectrometry (ESI-MS), circular dichroism (CD), and atomic force microscopy (AFM). The results lead to the working hypothesis that pH-dependent metal binding to Abeta1-40 may induce conformational changes, which affect the affinity toward other metals. A significant copper and zinc binding to Abeta1-40 peptide at pH 5.5 was found, whereas nickel ions commonly bind to each molecule of beta-amyloid peptide. Some complexes of Abeta1-40 with more than one nickel ion were identified by ESI-MS. In addition, nickel ions proved to enhance Abeta oligomerization. On increasing pH, up to 12 ions of zinc may bind to a single Abeta molecule. Under the same pH and concentration conditions, the binding pattern of the independent copper and silver ions to Abeta1-40 was different from that of the equimolecular mixture of the two metal ions. One might assume that some conformational changes due to water loss altered the capacity of Abeta peptide to bind certain heavy metal ions. As a consequence, copper-silver interaction with the binding process to Abeta1-40 became highly complex. A competition between silver and nickel ions for Abeta1-40 binding sites at high pH was also observed. New strategies were proposed to identify the characteristic signals for some important metal ion-peptide complexes in the spectra recorded at high pH or high concentrations of metal ions. To explain the formation of such a large number of high metal ion-Abeta complexes, we took into consideration the participation of both histidine residues and free amino groups as well as carboxylate ones in the binding process. Finally, CD and AFM studies supported the mass spectrometric data.
Drochioiu
Gabi
G
Al. I. Cuza University, Biochemistry Group, Iasi-700506, Romania. gabidr@uaic.ro
Manea
Marilena
M
Dragusanu
Mihaela
M
Murariu
Manuela
M
Dragan
Ecaterina Stela
ES
Petre
Brandusa Alina
BA
Mezo
Gabor
G
Przybylski
Michael
M
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008670:Metals / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D009532:Nickel / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D012834:Silver / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D015032:Zinc / Q000737:chemistry
D016229:Amyloid beta-Peptides; D008670:Metals; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D012834:Silver; D003300:Copper; D009532:Nickel; D015032:Zinc