title: Copper(II) complexes of peptide fragments of the prion protein. Conformation changes induced by copper(II) and the binding motif in C-terminal protein region.
abstract: In this paper, we report the characterization of copper(II) complexes with two prion (PrP) protein peptide fragment analogues (VNITKQHTVTTTT), one with the N-terminus acetylated and the C-terminus amidated (PrP Ac180-193NH2) and the other with both the C- and N-termini free (PrP 180-193). Such peptide sequence almost entirely encompasses the PrPC's helix 2 in the C-terminal region. The stoichiometry, the binding modes and the conformational features of the copper(II) complexes with the above mentioned two peptides were investigated by electrospray ionization-mass spectrometry (ESI-MS), UV-visible (UV-Vis) spectrometry and electron paramagnetic resonance (EPR) spectrometry as well as by circular dichroism (CD) measurements. The binding site location of copper(II) in the structured region of the protein can be here suggested on the basis of our findings that show the involvement of His 187 residue. The similarity of the EPR parameters suggests that the anchoring imidazole residue drives the copper(II) coordination environment towards a common binding motif in different regions of the prion protein.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
authors.forename: Valeria
authors.initials: V
authors.lastname: Guantieri
authors.forename: Giulia
authors.initials: G
authors.lastname: Grasso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Impellizzeri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pappalardo
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D006863:Hydrogen-Ion Concentration; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011138:Polytetrafluoroethylene / Q000737:chemistry; D011328:Prions / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D008667:Metalloproteins; D010446:Peptide Fragments; D011328:Prions; D003300:Copper; D011138:Polytetrafluoroethylene