title: Effect of metal ions on de novo aggregation of full-length prion protein.
abstract: It is well established that the prion protein (PrP) contains metal ion binding sites with specificity for copper. Changes in copper levels have been suggested to influence incubation time in experimental prion disease. Therefore, we studied the effect of heavy metal ions (Cu(2+), Mn(2+), Ni(2+), Co(2+), and Zn(2+)) in vitro in a model system that utilizes changes in the concentration of SDS to induce structural conversion and aggregation of recombinant PrP. To quantify and characterize PrP aggregates, we used fluorescently labelled PrP and cross-correlation analysis as well as scanning for intensely fluorescent targets in a confocal single molecule detection system. We found a specific strong pro-aggregatory effect of Mn(2+) at low micromolar concentrations that could be blocked by nanomolar concentration of Cu(2+). These findings suggest that metal ions such as copper and manganese may also affect PrP conversion in vivo.
authors.affiliation: Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität, München, Germany. Armin.Giese@med.uni-muenchen.de
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.forename: Johannes
authors.initials: J
authors.lastname: Levin
authors.forename: Uwe
authors.initials: U
authors.lastname: Bertsch
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
mesh_terms: D001665:Binding Sites; D019281:Dimerization; D007477:Ions; D046911:Macromolecular Substances; D019216:Metals, Heavy / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods
chemical_list: D007477:Ions; D046911:Macromolecular Substances; D019216:Metals, Heavy; D011328:Prions; D011994:Recombinant Proteins