NR AXUI
AU Peretz,D.; Lau,A.; Yam,A.; Wang,X.; Gao,C.; Timoteo,G.; Chien,D.; Wu,P.
TI Characterization of Human PrP-derived Peptides that Discriminate Full-length PrPsc from PrPc
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.35
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Upon our initial discovery that PrP-derived peptides were capable of capturing the pathogenic prion protein (PrPsc), we have been interested in how these peptides interact with PrPsc. After screening peptides from the entire human PrP sequence, we found two peptides (PrP19-30 and PrP100-111) capable of binding full-length PrPsc in plasma, with greater than 3000-fold binding specificity to PrPsc over the normal prion protein (PrPc). To detect captured PrPsc, we have developed a highly sensitive sandwich ELISA with a limit of detection of 4 attomoles (0.5 pg/mL) of human rPrP. Through extensive analyses we show that positively charged amino acids play an important, but not exclusive, role in the interaction between the peptides and PrPsc. Neither hydrophobic nor polar interactions appear to correlate with binding activity. The peptide:PrPsc interaction was not sequence specific, but amino acid composition affected binding. Binding occurs through a conformational domain that is only present in PrPsc, is species independent, and is not affected by proteinase K digestion. These two positively charged domains have been reported to be important for prion propagation through a variety of prion transmission studies. Taken together, these findings suggest a mechanism where cationic domains of PrPc may play a role in the recruitment of PrPc to PrPsc.
AD D. Peretz, A. Lau, A. Yam, X. Wang, C. Gao, G. Timoteo, D. Chien, P. Wu, Novartis, USA
SP englisch
PO Schottland
EA pdf-Datei und Poster (Erstautor auf D. Peretz geändert und Titel zur Klarstellung des vCJD-Bezugs ergänzt)