NR ARCY
AU Dumpitak,C.; Stoehr,J.; Elfrink,K.; Leffers,K.W.; Riesner,D.
TI Structural transition and prion-specific secondary components in prion protein conversion
QU TSE-Forum, 4. Kongress - Nationale TSE-Forschungsplattform, Düsseldorf 28.10.-29.10.2004, Vortrag V-15
PT Konferenz-Vortrag
AB
Structural transition of soluble, alpha-helical, protease sensitive and non-infectious prion protein (PrP) to insoluble, protease resistant, predominantly beta structured and infectious PrP is the main event in prion amplification and pathogenesis. Understanding the mechanism of the transformation process as well as the influences of secondary components found in natural prions is essential to understand prion diseases.
To study those processes we applied an in vitro transition system developed by our group (1, 2): Depending upon submicellar concentrations of sodiumdodecylsulfate (SDS) PrP is present in soluble, PK-sensitive, alpha-helical monomers or dimers, soluble ß-structured oligomers or insoluble, partially PK-resistant, ß-structured multimers. Under particular conditions amyloid fibrils could be generated. Those fibrils were generated from recombinant PrP, but also from solubilized PrP 27-30 or PrPc from the brains of non-infected hamsters. We have isolated PrPc from CHO-cells for biophysical studies and could demonstrate the specific N-terminal cleavage after aggregate formation analogous to the cleavage of PrPsc to PrP 27-30. Since specific lipids (4) and a polyglucose scaffold (5) were detected in natural prions, we studied the influence of these secondary components on the conformational transitions of PrP.
(1) Post K., Pitschke M., Schäfer O., Wille H., Appel T. R., Kirsch D., Mehlhorn I., Serban H., Prusiner S. B. & Riesner D. (1998). Biol. Chem. 379: 1307-1317
(2) Jansen K., Schäfer O., Birkmann E., Post K., Seban H., Prusiner S. B. & Riesner D. (2001). Biol. Chem. 382: 683-691.
(3) Elfrink K. & Riesner D. (2004) in: Methods and tools in Biosciences and Medicine - Techniques in prion research, Lehmann S. & Grassi J. (eds.), Birkhäuser Verlag
(4) Klein T R, Kirsch D, Kaufmann R and Riesner D (1998). Biol. Chem. 379: 655-666.
(5) Appel T R, Dumpitak C, Matthiesen U and Riesner D (1999). Biol. Chem. 380: 1295-1306.
AD C. Dumpitak, J. Stoehr, K. Elfrink, K.-W. Leffers & D. Riesner, Institut für Physikalische Biologie and Biologisch-Medizinisches-Forschungszentrum, Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany
SP englisch
PO Deutschland
OR Tagungsband