J Neurochem. 1999 Sep;73(3):1288-92.

Cysteine 144 is a key residue in the copper reduction by the beta-amyloid precursor protein.

Ruiz FH, González M, Bodini M, Opazo C, Inestrosa NC.

Source

Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Santiago, Chile.

Abstract

The beta-amyloid precursor protein (beta-APP) contains a copper-binding site localized between amino acids 135 and 156 (beta-APP(135-156)). We have employed synthetic beta-APP peptides to characterize their capacities to reduce Cu(II) to Cu(I). Analogues of the wild-type beta-APP(135-156) peptide, containing specific amino acid substitutions, were used to establish which residues are specifically involved in the reduction of copper by beta-APP(135-156). We report here that beta-APP's copper-binding domain reduced Cu(II) to Cu(I). The single-mutant beta-APP(His147-->Ala) and the double-mutant beta-APP(His147-->Ala/His149-->Ala) showed a small decrease in copper reduction in relation to the wild-type peptide and the beta-APP(Cys144-->Ser) mutation abolished it, suggesting that Cys144 is the key amino acid in the oxidoreduction reaction. Our results confirm that soluble beta-APP is involved in the reduction of Cu(II) to Cu(I).

PMID:: 10461923; [PubMed - indexed for MEDLINE]

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