title: Copper(II) sequentially loads onto the N-terminal amino group of the cellular prion protein before the individual octarepeats.
abstract: The cellular prion protein (PrPC) binds to Cu2+ ions in vivo, and a misfolded form of PrPC is responsible for a range of transmissible spongiform encephalopathies. Recently, disruption of Cu2+ homeostasis in mice has been shown to impart resistance to scrapie infection. Using full-length PrPC and model peptide fragments, we monitor the sequential loading of Cu2+ ions onto PrPC using visible circular dichroism. We show the N-terminal amino group of PrPC is not the principal binding site for Cu2+; however, surprisingly, it has an affinity for Cu2+ tighter than that of the individual octarepeat binding sites present within PrPC. We re-evaluate what is understood about the sequential loading of Cu2+ onto the full-length protein and show for the first time that Cu2+ loads onto the N-terminal amino group before the single octarepeat binding sites.
authors.forename: Helen F
authors.initials: HF
authors.lastname: Stanyon
authors.forename: Khushbu
authors.initials: K
authors.lastname: Patel
authors.forename: Nadia
authors.initials: N
authors.lastname: Begum
authors.forename: John H
authors.initials: JH
authors.lastname: Viles
mesh_terms: D000818:Animals; D001665:Binding Sites; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D051379:Mice; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D011328:Prions / Q000737:chemistry
chemical_list: D018621:PrPC Proteins; D011328:Prions; D003300:Copper