title: A direct determination of the dissociation constant for the Cu(II) complex of amyloid beta 1-40 peptide.
abstract: Interactions of amyloid beta (Abeta) peptides with Cu(II) are believed to play a crucial role in the molecular mechanisms of neurotoxicity of Alzheimer's disease. There is, however, a serious disagreement regarding the strength of Cu(II) binding to these peptides. We used recombinant amyloid beta peptide 1-40 (Abeta40) to determine the stoichiometry and dissociation constants of Cu(II)-Abeta40 complexes using fluorescence spectroscopy. A single Cu(Abeta40) complex, characterized with the conditional dissociation constant K(d)(cond) = 57 +/- 5 nM was identified. This complex does not bind Hepes buffer molecules, as indicated by the total lack of relationship between K(d)(cond) values and Hepes concentration. The differences between this and other determinations of this constant and its relevance for the understanding of Cu(II) interaction with Abeta peptides are discussed.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Rózga
authors.forename: Marcin
authors.initials: M
authors.lastname: Kłoniecki
authors.forename: Michał
authors.initials: M
authors.lastname: Dadlez
authors.forename: Wojciech
authors.initials: W
authors.lastname: Bal
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D003300:Copper