title: Identification of a novel high affinity copper binding site in the APP(145-155) fragment of amyloid precursor protein.
abstract: The copper(II) binding features of the APP(145-155) and APP(145-157) fragments of the amyloid precursor protein, Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-NH2 and Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH2 were studied by NMR spectroscopy and NMR findings were supported by UV-vis, CD and EPR spectra. Potentiometric measurements were performed only for the more soluble Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH2 peptide fragment. The following was shown: (i) the imidazole rings of all the three His residues are involved in metal coordination; (ii) metal binding induces ionisation of Leu-148 and His-149 amide nitrogens that complete the donor set to copper(II) in the species dominant at neutral pH; (iii) the unusual coordination scheme of the His-Xxx-His-Xxx-His consensus sequence justifies the high specificity for Cu(II) when compared to SOD-like or albumin-like peptides or even in amyloid Abeta fragments. The present findings may represent the key for interpreting the observed requirement of His residues conservation for the redox cycling between Cu(II) and Cu(I) by soluble APP.
authors.affiliation: Department of Chemistry and the NMR Center, University of Siena, via Moro, 53100 Siena, Italy. valensin@unisi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Valensin
authors.forename: Francesca Maria
authors.initials: FM
authors.lastname: Mancini
authors.forename: Marek
authors.initials: M
authors.lastname: Łuczkowski
authors.forename: Anna
authors.initials: A
authors.lastname: Janicka
authors.forename: Kornelia
authors.initials: K
authors.lastname: Wisniewska
authors.forename: Elena
authors.initials: E
authors.lastname: Gaggelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Valensin
authors.forename: Leszek
authors.initials: L
authors.lastname: Łankiewicz
authors.forename: Henryk
authors.initials: H
authors.lastname: Kozlowski
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D003300:Copper