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

Ruiz F.H.; Opazo C.; Inestrosa, N. C.; Bodini, M; Gonzalez, M.

Keywords: copper, oxidation, acid, amyloid, reduction, protein, structure, disease, peptide, mutation, substitution, humans, cysteine, fragments, domain, beta-protein, article, precursor, alzheimer, potentiometry, amino, priority, Reaction, journal, synthetic, Oxidation-Reduction

Abstract

The ?-amyloid precursor protein (?-APP) contains a copper-binding site localized between amino acids 135 and 156 (?-APP135-156). We have employed synthetic ?-APP peptides to characterize their capacities to reduce Cu(II) to Cu(I). Analogues of the wild-type ?-APP135-156 peptide, containing specific amino acid substitutions, were used to establish which residues are specifically involved in the reduction of copper by ?- APP135-156. We report here that ?-APP's copper-binding domain reduced Cu(II) to Cu(I). The single-mutant ?-APP(His147?Ala) and the double-mutant ?-APP(His147?Ala/His149?Ala) showed a small decrease in copper reduction in relation to the wild-type peptide and the ?-APP(Cys144?Ser) mutation abolished it, suggesting that Cys144 is the key amino acid in the oxidoreduction reaction. Our results confirm that soluble ?-APP is involved in the reduction of Cu(II) to Cu(I).

Más información

Título de la Revista: JOURNAL OF NEUROCHEMISTRY
Volumen: 73
Número: 3
Editorial: Wiley
Fecha de publicación: 1999
Página de inicio: 1288
Página final: 1292
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0345035452&partnerID=q2rCbXpz