title: Copper binding to chicken and human prion protein amylodogenic regions: differences and similarities revealed by Ni2+ as a diamagnetic probe.
abstract: Both human (h) and chicken (Ch) prion proteins (PrP) bind copper ions within the so called "tandem repeat" N-terminal region. Outside this region, hPrP possesses two additional copper binding sites, localized at His-96 and His-111 in the so called "amylodogenic" or neurotoxic region (residues 91-126). Also ChPrP possesses a similar region (ChPrP(105-140)) containing two His (His-110 and His-124) and an identical hydrophobic tail of 15 amino acids rich in Ala and Gly. The copper binding abilities within such region of ChPrP were investigated by NMR, CD and potentiometry using Ni(2+) as diamagnetic probe. The formation of diamagnetic metal complexes allowed to monitor the chemical shift and signal intensity variations and to determine the structural and kinetic features of the His-110 and His-124 metal binding sites. Finally a comparison between the hPrP and ChPrP metal binding abilities was performed. We found that the two prion proteins exhibited different copper and nickel preferences with the favoured metal binding sites localized at opposite His: His-110 for ChPrP, and His-111 for hPrP.
authors.affiliation: Department of Chemistry, University of Siena, Via Aldo Moro 53-100 Siena, Italy. valensindan@unisi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Valensin
authors.forename: Karolina
authors.initials: K
authors.lastname: Gajda
authors.forename: Ewa
authors.initials: E
authors.lastname: Gralka
authors.forename: Gianni
authors.initials: G
authors.lastname: Valensin
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Henryk
authors.initials: H
authors.lastname: Kozlowski
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002645:Chickens; D003300:Copper / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009532:Nickel / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D016415:Sequence Alignment
chemical_list: D000682:Amyloid; D010446:Peptide Fragments; D011328:Prions; D003300:Copper; D009532:Nickel