title: Copper(II) coordination outside the tandem repeat region of an unstructured domain of chicken prion protein.
abstract: Combined potentiometric, calorimetric and spectroscopic methods were used to investigate the Cu(2+) binding ability and coordination behaviour of some peptide fragments related to the neurotoxic region of chicken Prion Protein. The systems studied were the following protein fragments: chPrP(106-114), chPrP(119-126), chPrP(108-127), chPrP(105-127) and chPrP(105-133).The complex formation always starts around pH 4 with the coordination of an imidazole nitrogen, followed by the deprotonation and binding of amide nitrogens from the peptidic backbone. At neutral pH, the {N(im), 3N(-)} binding mode is the preferred one. The amide nitrogens participating in the binding to the Cu(2+) ion derive from residues from the N-terminus side, with the formation of a six-membered chelate ring with the imidazolic side chain.Comparison of thermodynamic data for the two histydyl binding domains (around His-110 and His-124), clearly indicates that the closest to the hexarepeat domain (His-110) has the highest ability to bind Cu(2+) ions, although both of them have the same coordination mode. Conversely, in the case of the human neurotoxic peptide region, between the two binding sites, located at His-96 and His-111, the farthest from the tandem repeat region is the strongest one. Finally, thermodynamic data show that chicken peptide is a distinctly better ligand for coordination of copper ions with respect to the human fragment.
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Gralka
authors.forename: Daniela
authors.initials: D
authors.lastname: Valensin
authors.forename: Karolina
authors.initials: K
authors.lastname: Gajda
authors.forename: Dimitri
authors.initials: D
authors.lastname: Bacco
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szyrwiel
authors.forename: Maurizio
authors.initials: M
authors.lastname: Remelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Valensin
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamasz
authors.forename: Wioletta
authors.initials: W
authors.lastname: Baranska-Rybak
authors.forename: Henryk
authors.initials: H
authors.lastname: Kozłowski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002645:Chickens / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid
chemical_list: D010446:Peptide Fragments; D011328:Prions; D003300:Copper