title: Investigation of Cu2+ binding to human and rat amyloid fragments Aβ (1-16) with a protein nanopore.
abstract: Recent evidence shows that metal coordination by amyloid beta peptides (Aβ) determines structural alterations of peptides, and His-13 from Aβ is crucial for Cu(2+) binding. This study used the truncated, more soluble Aβ1-16 isoforms derived from human and rat amyloid peptides to explore their interaction with Cu(2+) by employing the membrane-immobilized α-hemolysin (α-HL) protein as a nanoscopic probe in conjunction with single-molecule electrophysiology techniques. Unexpectedly, the experimental data suggest that unlike the case of the human Aβ1-16 peptide, Cu(2+) complexation by its rat counterpart leads to an augmented association and dissociation kinetics of the peptide reversible interaction with the protein pore, as compared to the Cu(2+)-free peptide. Single-molecule electrophysiology data reveal that both human and rat Cu(2+)-complexed Aβ peptides induce a higher degree of current flow obstruction through the α-HL pore, as compared to the Cu(2+)-free peptides. It is suggested that morphology changes brought by Cu(2+) binding to such amyloidic fragments depend crucially upon the presence of the His-13 residue on the primary sequence of such peptide fragments, and the α-HL protein-based approach provides unique opportunities and challenges to probing metal-induced folding of peptides.
authors.affiliation: Department of Interdisciplinary Research and ‡Department of Physics, Laboratory of Molecular Biophysics and Medical Physics, Alexandru Ioan Cuza University , Boulevard Carol I, No. 11, Iasi 700506, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Asandei
authors.forename: Irina
authors.initials: I
authors.lastname: Schiopu
authors.forename: Sorana
authors.initials: S
authors.lastname: Iftemi
authors.forename: Loredana
authors.initials: L
authors.lastname: Mereuta
authors.forename: Tudor
authors.initials: T
authors.lastname: Luchian
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D003300:Copper / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D058608:Nanopores; D011485:Protein Binding; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D003300:Copper