Zinc binding to Alzheimer's Abeta(1-16) peptide results in stable soluble complex.
Aggregation of the human amyloid beta-peptide (Abeta) into insoluble plaques is a key event in Alzheimer's disease. Zinc sharply accelerates the Abeta aggregation in vitro, and the Abeta region 6-28 was suggested to be the obligatory zinc binding site. However, time-dependent aggregation of the zinc-bound Abeta species investigated so far prevented their structural analysis. By using CD spectroscopy, we have shown here for the first time that (i) the protected synthetic peptide spanning the fragment 1-16 of Abeta binds specifically zinc with 1:1 and 1:2 stoichiometry under physiologically relevant conditions; (ii) the peptide-zinc complex is soluble and stable for several months; (iii) zinc binding causes a conformational change of the peptide towards a more structured state. These findings suggest the region 1-16 to be the minimal autonomous zinc binding domain of Abeta.
Kozin
S A
SA
INRA 806/EA2703 MNHN, Institut de Biologie Physico-Chimique, 13, rue P. et M. Curie, Paris, 75005, France.
Zirah
S
S
Rebuffat
S
S
Hoa
G H
GH
Debey
P
P
D000544:Alzheimer Disease / Q000209:etiology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001665:Binding Sites; D002413:Cations, Divalent / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015032:Zinc / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D010446:Peptide Fragments; C433241:amyloid beta-protein (1-16); D015032:Zinc