NR ATFM
AU Riesner,D.
TI Conformational transitions and membrane interaction of posttransitionally modified PrP
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-17
PT Konferenz-Vortrag
AB The molecular mechanism of prion infections is the transformation of the membrane-bound cellular prion protein PrPc into the amyloidic and pathogenic isoform PrPsc and the transformation induced by the invading PrPsc-particle. On the pathway of transformation several intermediates can be identified and characterized by biophysical methods. Although mouse rec PrP(89-230) in a fibrillar conformation was shown to be infectious (Legname G, et al.; 2004; Science 305: 673-676) natural prions contain PrP with GPI-anchor, N-glycosylgroups and non-covalently bound components like particular lipids and a glycogen-like scaffold (Dumpitak C, et al.; 2005; Biol. Chem, in press). With PrPc isolated from CHO-cells the equilibrium between membrane-bound PrPc and PrPc free in solution was determined resulting in concentrations of 10-20-10-8 M free PrPc. Free PrP can form alpha-helical monomers and dimers and can undergo in dependence upon the solution conditions a cooperative transition into ß-sheet rich oligomers and large insoluble aggregates. If a partially denatured intermediate between the dimer and the oligomer is stabilized for long time, highly structured fibrils are formed with high similarity to the infectious fibrils mentioned above (Leffers K-W, et al.; 2004; JMB 344:839-853; Leffers K-W, et al.;2005; Biol. Chem.386: 569-580). The secondary components like lipids and glycogen-like scaffold accelerate fibril formation. Under particular solution conditions fibril formation can be suppressed completely or induced effectively by minute amounts of PrPsc-seeds.
AD D.Riesner, Institut für Physikalische Biologie and Biologisch-Medizinisches-Forschungszentrum, Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany
SP englisch
PO Deutschland