title: On the ability of CuAβ1-x peptides to form ternary complexes: Neurotransmitter glutamate is a competitor while not a ternary partner.
abstract: In the light of conflicting reports on the ability of copper(II) complexes of amyloid beta (Aβ) peptides to form ternary complexes with small molecules co-present in the biological milieu, we performed a study of coordination equilibria in the system containing Cu(II) ions, the Aβ1-16 peptide, glutamic acid and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid, HEPES) buffer. Using potentiometry, isothermal titration calorimetry (ITC), UV-visible spectroscopy and EPR, we concluded that glutamic acid was not able to form such a ternary complex, but can efficiently compete for the Cu(II) ion with the Aβ peptide at Glu concentrations relevant for the synaptic cleft. We also found that the literature constants for Cu(II) complexes with Glu were overestimated, but this effect was partially compensated by the formation of a ternary Cu(Glu)(HEPES) complex. Our results indicate that small molecules co-present with Cu(II) ions and Aβ peptides in the synaptic cleft are not very likely to enhance Cu(II)/Aβ interactions, but instead should be considered as a Cu(II) buffering system that may help prevent these interactions and participate in Cu(II) clearance from the synaptic cleft.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Frączyk
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Izabela A
authors.initials: IA
authors.lastname: Zawisza
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Goch
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: Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Drew
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland. Electronic address: wbal@ibb.waw.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Bal
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry*; D018377:Neurotransmitter Agents / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D018377:Neurotransmitter Agents; D010455:Peptides; D018698:Glutamic Acid; D003300:Copper
keywords: Cu(II)-Aβ complexes; glutamic acid; ternary complexes