title: Truncated prion protein PrP226* - A structural view on its role in amyloid disease.
abstract: In the brain of patients with transmissible spongiform encephalopathies, besides PrPScaggregates, deposition of truncated PrP molecules was described. Jansen et al. reported two clinical cases with deposition of C-terminally truncated PrP, one of them ending with Tyr226. We have previously described the discovery of monoclonal antibody V5B2 that selectively recognizes this version of the prion protein, which we called PrP226*. Using monoclonal antibody V5B2 we showed that accumulation of PrP226* is characteristic for most types of human and animal TSEs. Its distribution correlates to the distribution of PrPScaggregates. To gain insight into the structural basis of its presence and distribution in PrP aggregates, we have determined the NMR structure of recombinant PrP226*. The structure of the protein consists of a disordered N-terminal part (residues 90-125) and a structured C-terminal part (residues 126-226). The C-terminal segment consists of four α-helices and a short antiparallel β-sheet. Our model predicts a break in the C-terminal helix and reorganized hydrophobic interactions between helix α3and β2-α2loop due to the shorter C-terminus. The structural model gives information on the possible role of the protein in the development of amyloid disease and can serve as a foundation to develop tools for prevention and treatment of prion diseases.
authors.affiliation: Department for the Production of Diagnostic Reagents and Research & R&D Service, Blood Transfusion Centre of Slovenia, Šlajmerjeva 6, SI-1000 Ljubljana, Slovenia. Electronic address: valerija.kovac@ztm.si.
authors.forename: Valerija
authors.initials: V
authors.lastname: Kovač
authors.affiliation: Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
authors.forename: Blaž
authors.initials: B
authors.lastname: Zupančič
authors.affiliation: Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia; EN-FIST Centre of Excellence, Dunajska 156, SI-1001 Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Ilc
authors.affiliation: Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia; EN-FIST Centre of Excellence, Dunajska 156, SI-1001 Ljubljana, Slovenia; Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Plavec
authors.affiliation: Department for the Production of Diagnostic Reagents and Research & R&D Service, Blood Transfusion Centre of Slovenia, Šlajmerjeva 6, SI-1000 Ljubljana, Slovenia.
authors.forename: Vladka
authors.initials: V
authors.lastname: Čurin Šerbec
mesh_terms: D000686:Amyloidosis / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019906:Nuclear Magnetic Resonance, Biomolecular; D000072002:Prion Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000072002:Prion Proteins
keywords: NMR structure; Prion protein; Stop mutation; Truncation