NR AXQH
AU Krammer,C.; Suhre,M.H.; Diemer,C.; Hess,S.; Schätzl,H.; Scheibel,T.; Vorberg,I.
TI Fusion with Yeast Sup35p-NM Modulates Cytosolic PrP Aggregation in Mammalian Cells
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.72
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB In mammalian prion diseases, an abnormally folded, aggregated form of the prion protein (PrPsc) appears to catalyze a conformational switch of its cellular isoform (PrPc) to an aggregated state. A similar prion-like phenomenon has been reported for the Saccharomyces cerevisiae translation termination factor Sup35p that can adopt a self-propagating conformation. We have compared aggregation propensities of chimeric proteins derived from the Sup35p prion domain NM and PrP in the cytosol of mammalian cells. Here we demonstrate that cytosolic Sup35p-NM and PrP display strikingly different aggregation behaviours, with Sup35p-NM remaining soluble and cytosolic PrP readily aggregating. Notably, fusion of domains NM and/or N with PrP strongly modulated frequency and size of the aggregates. NM-PrP chimera formed huge aggregates reminiscent of coalescent NM aggregates found in yeast cells displaying the [PSI+] prion phenotype. In parallel, we investigated aggregation propensities of NM and NM-PrP in vitro. While NM readily self-assembled into fibrils, NM-PrP fibrillization depended on induction by agitation. Thus, our results provide new insights into protein aggregation behaviours, suggesting that aggregation of yeast and mammalian prion proteins in the cytosol of mammalian cells is strongly influenced by cellular conditions or factors that either inhibit or promote accumulation of these aggregation-prone proteins.
AD C. Krammer, C. Diemer, H. Schätzl, I. Vorberg, Institute of Virology, Prion Research Group, Germany; M.H. Suhre, S. Hess, T. Scheibel, Lehrstuhl für Biotechnologie, Technical University of Munich, Department Chemie, Germany
SP englisch
PO Schottland
EA pdf-Datei und Poster (Autorenliste um E. Kremmer ergänzt und geringfügige Änderung der Reihenfolge der Autoren)