Histidine-13 Is a Crucial Residue in the Zinc Ion-Induced Aggregation of the Aβ Peptide of Alzheimer's Disease
- 30 June 1999
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 38 (29) , 9373-9378
- https://doi.org/10.1021/bi990205o
Abstract
Metal ions such as Zn2+ and Cu2+ have been implicated in both the aggregation and neurotoxicity of the β-amyloid (Aβ) peptide that is present in the brains of Alzheimer's sufferers. Zinc ions in particular have been shown to induce rapid aggregation of Aβ. Rat Aβ binds zinc ions much less avidly than human Aβ, and rats do not form cerebral Aβ amyloid. Rat Aβ differs from human Aβ by the substitution of Gly for Arg, Phe for Tyr, and Arg for His at positions 5, 10, and 13, respectively. Through the use of synthetic peptides corresponding to the first 28 residues of human Aβ, rat Aβ, and single-residue variations, we use circular dichroism spectroscopy, sedimentation assays, and immobilized metal ion affinity chromatography to show that the substitution of Arg for His-13 is responsible for the different Zn2+-induced aggregation behavior of rat and human Aβ. The coordination of Zn2+ to histidine-13 is critical to the zinc ion induced aggregation of Aβ.Keywords
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