NR ATRH
AU Gobbi,M.; Colombo,L.; Manzoni,C.; Morbin,M.; Vanoni,M.; Del Favero,E.; Cantu,L.; Forloni,G.; Tagliavini,F.; Salmona,M.
TI Gerstmann-Sträussler-Scheinker disease amyloid protein polymerizes according to the "dock-and-lock" model
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-23
PT Konferenz-Poster
AB Prion protein (PrP) amyloid formation is a central feature of genetic and acquired prion diseases such as Gerstmann-Sträussler-Scheinker disease (GSS). The major component of GSS amyloid is a PrP fragment spanning residues ~82-146 which, when synthesized as a peptide, adopts a secondary structure primarily in beta-sheet and readily forms fibrils with features of GSS amyloid. Understanding the early phases of misfolding and aggregation is important for the development of prevention strategies. Since evidence suggest the neuropathological role of prefibrillar oligomers rather than mature fibrils, we employed surface plasmon resonance (SPR) to characterize the binding events underlying PrP82-146 oligomerization at the first stages of the process. To this aim we followed in real-time the binding reactions occurring during short-term addition of PrP82-146 small oligomers (1-5mers, flowing species), onto soluble prefibrillar PrP82-146 aggregates immobilized on the sensor chip. SPR studies suggest efficient aggregation/elongation and could be adequately fitted by the equation modelling the dock-and-lock mechanism of polymerization, in which the locking step is due to sequential conformational changes increasing the affinity of the monomer for the fibril until to condition of irreversible binding is reached. The comparison of the kinetic parameters, previously obtained with Abeta, suggests that PrP82-146 has a greater propensity to polymerize and forms more stable aggregates.
AD Marco Gobbi, Laura Colombo, Claudia Manzoni, Gianluigi Forloni, Mario Salmona, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy; Michela Morbin, Fabrizio Tagliavini, Istituto Nazionale Neurologico Carlo Besta, Milano, Italy; Marco Vanoni, Università di Milano-Bicocca, Milano, Italy; Elena Del Favero, Laura Cantù, Università degli Studi di Milano, Milano, Italy
SP englisch
PO Deutschland