NR AXQK
AU Krautler,N.J.; Calella,A.M.; Rutishauser,D.; Baumann,F.; Polymenidou,M.; Aguzzi,A.
TI The Prion Protein Interactome during Health and Disease - A Proteomic Analysis
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.19
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The prion protein (PrP) is thought to be a signaling molecule, yet none of the components mediating its signals have been identified. Recently it was demonstrated that deletions within the central domain of PrP (amino acids 94-134, PrPdCD) trigger fatal neuropathological effects (Baumann et al., 2007), while more amino-proximal truncations lacking the octarepeat region have no obvious phenotype (Shmerling et al., 1998). Importantly, toxicity of PrPdCD could be reversed by co-expression of full-length PrP in a dose-dependent manner. These results suggested that full-length PrP and PrPdCD could assemble into distinct higher molecular weight protein complexes. The aim of this study is to purify the protein complex associated with full-length PrP or the deletion mutant PrPdCD from membrane preparations of the brain and analyze its
composition. Isolation is achieved by co-immunoprecipitation using the monoclonal PrP antibody POM2 generated in our laboratory, which binds with high affinity to defined epitopes of PrP and PrPdCD. Specific elution of the complexes after
immunoprecipitation is enabled using epitope-mimicking peptides that compete for the binding to the POM2 antibody. PrP-associated proteins are currently analyzed by ITRAQ or 1D SDS-PAGE in combination with mass spectrometry. With the identification of proteins associated with PrP and PrPdCD, we aim to determine the
components essential for the physiological signaling as well as the factor(s) inducing the fatal phenotype. Understanding the molecular basis of PrPdCD toxicity might provide a deeper insight into the mechanisms underlying prion pathology.
AD N. Krautler, A.-M. Calella, D. Rutishauser, F. Baumann, M. Polymenidou, A. Aguzzi, Institute of Neuropathology, University Hospital Zürich, Switzerland
SP englisch
PO Schottland