title: Resistance of Cu(Aβ4-16) to Copper Capture by Metallothionein-3 Supports a Function for the Aβ4-42 Peptide as a Synaptic Cu(II) Scavenger.
abstract: Aβ4-42 is a major species of Aβ peptide in the brains of both healthy individuals and those affected by Alzheimer's disease. It has recently been demonstrated to bind Cu(II) with an affinity approximately 3000 times higher than the commonly studied Aβ1-42 and Aβ1-40 peptides, which are implicated in the pathogenesis of Alzheimer's disease. Metallothionein-3, a protein considered to orchestrate copper and zinc metabolism in the brain and provide antioxidant protection, was shown to extract Cu(II) from Aβ1-40 when acting in its native Zn7 MT-3 form. This reaction is assumed to underlie the neuroprotective effect of Zn7 MT-3 against Aβ toxicity. In this work, we used the truncated model peptides Aβ1-16 and Aβ4-16 to demonstrate that the high-affinity Cu(II) complex of Aβ4-16 is resistant to Zn7 MT-3 reactivity. This indicates that the analogous complex of the full-length peptide Cu(Aβ4-42) will not yield copper to MT-3 in the brain, thus supporting the concept of a physiological role for Aβ4-42 as a Cu(II) scavenger in the synaptic cleft.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106, Warsaw, Poland.
authors.forename: Nina E
authors.initials: NE
authors.lastname: Wezynfeld
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106, Warsaw, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Stefaniak
authors.affiliation: Laboratory of Chemical Biology, University of Wrocław, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Stachucy
authors.affiliation: Laboratory of Chemical Biology, University of Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Drozd
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106, Warsaw, Poland.
authors.forename: Dawid
authors.initials: D
authors.lastname: Płonka
authors.affiliation: Florey Department of Neuroscience and Mental Health, The University of Melbourne, Australia.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Drew
authors.affiliation: Laboratory of Chemical Biology, University of Wrocław, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Krężel
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106, Warsaw, Poland. wbal@ibb.waw.pl.
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*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism*; D000090023:Metallothionein 3; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D003300:Copper; D015032:Zinc
keywords: amyloid-beta peptides; copper; metalloproteins; metallothionein; zinc