NR ATRP
AU Viehrig,C.; Ziegler,J.; Roesch,P.; Schwarzinger,S.
TI On Putative Aggregation Sites in Human Prion Protein
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-31
AD C.Viehrig, J.Ziegler, P.Roesch, S.Schwarzinger, University Bayreuth, Germany
PT Konferenz-Poster
AB Prion diseases are associated with a conformational change of the cellular prion protein, PrPc, into its pathogenic conformer, PrPsc. It is assumed that different conformers of PrPsc are responsible for the different strains observed in prion diseases. In order to identify putative aggregation initiation sites we have investigated the aggregation kinetics and morphologies of aggregates of various peptides within residues 106 and 157 of the sequence of the human prion protein. Our data indicate that the alanine rich region (A113-GAAAAG-A120), which is conformationally rather flexible, requires an adjacent part of the sequence containing hydrophobic and bulky residues for proper fibril formation. We also identified the sequence I138-ICH-F141, which is presented at the surface of PrPc in a beta-like, extended conformation and which has a preference for extended, beta-like conformations in the disordered state (Ziegler et al., JBC, 2003), as an potential aggregation initiation site. A short peptide containing this sequence forms highly ordered aggregates on a fast timescale. A recent simulation of the PrPc -> PrPsc transitions (DeMarco and Daggett, PNAS, 2004) shows that this sequence is part of a beta-strand, which is involved in intermolecular PrPsc-PrPsc contacts.
SP englisch
PO Deutschland