NR APAS
AU Zahn,R.
TI The Octapeptide Repeats in Mammalian Prion Protein Constitute a pH-dependent Aggregation Site
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-09
PT Konferenz-Poster
AB Structural studies of mammalian prion protein at pH values between 4.5 and 5.5 established that the N-terminal 100-residue domain is flexibly disordered. Here we show that at pH values between 6.5 and 7.8, i.e., the pH at the cell membrane, the octapeptide repeats in recombinant human prion protein hPrP(23-230) encompassing the highly conserved sequence PHGGGWGQ are structured. The nuclear magnetic resonance solution structure of the OPR at pH 6.2 reveals a new structural motif that causes a reversible pH-dependent PrP oligomerization into macromolecular aggregates. Comparison with the crystal structure of HGGGW-Cu2+ indicates that the binding of copper ions induces a conformational transition that presumably modulates PrP aggregation. The immobilization of the cellular prion protein to the cell surface along with these results suggests a functional role in homophylic cell adhesion.
AD Ralph Zahn, Molekularbiologie und Biophysik, ETH Zürich, Switzerland
SP englisch
PO Deutschland