title: Prion protein fate governed by metal binding.
abstract: The conversion of the normal cellular prion protein to an abnormal isoform is considered to be causal to the prion diseases or transmissible spongiform encephalopathies. The prion protein is a copper binding protein but under some conditions may bind other metals. In particular, the binding of manganese has been suggested to convert the prion protein (PrP) to a protease resistant isoform. Therefore, the differences in the way the protein binds copper and manganese might be revealing in terms of the mechanism of conversion of the protein or its normal cellular activity. We report the use of near-infrared spectroscopy for studies on aqueous solutions of prion protein binding Cu or Mn. These alloforms of the protein were analyzed by spectral data acquisition and multivariate analysis. Our results indicate that PrP binds both Mn and Cu differently. Analyses of Cu binding suggest that the PrP-Cu complex protected Cu from the water increasing protein stability. PrP-Mn does not protect Mn from water interactions. A real-time study of the protein alloforms showed that PrP-Cu remains stable in solution, but that PrP-Mn underwent highly different changes that led to fibril formation.
authors.affiliation: Department of Bioproduction Engineering, Faculty of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Roumiana N
authors.initials: RN
authors.lastname: Tsenkova
authors.forename: Ilina K
authors.initials: IK
authors.lastname: Iordanova
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Toyoda
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
mesh_terms: D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D008345:Manganese / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms; D012996:Solutions; D013055:Spectrophotometry, Infrared / Q000379:methods*; D014867:Water / Q000737:chemistry*
chemical_list: D046911:Macromolecular Substances; D008670:Metals; D011328:Prions; D020033:Protein Isoforms; D012996:Solutions; D014867:Water; D008345:Manganese; D003300:Copper