NR AXVJ
AU Rost,R.; Gädtke,L.; Maas,E.; Groschup,M.H.; Schätzl,H.; Vorberg,I.
TI PrP Species Specific Amino Acid Residues Located on the Outer Surfaces of Helix 2 and 3 Critically Affect Prion Infection
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.07
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Cell culture models for prion diseases have greatly helped us to understand the role of the prion protein (PrP) amino acid sequence for the prion species barrier. However, so far comparative studies on the direct influence of PrP alterations on the prion infection process (as opposed to studies in persistently infected cell cultures) was mainly restricted to transgenic animal models. One reason for this is that all so far identified cell lines susceptible to prions code for endogenous wild-type PrP. Thus, successful infection could still be supported by endogenous PrP expression rather than by transgenic PrP. We have recently shown that the prion protein knock-out cell line HpL3-4 can be rendered permissive to prion infection by ectopic expression of PrP. This system was used to study the influence of sheep PrP specific residues in mouse PrP on the infection process with mouse adapted scrapie. Our studies reveal several critical residues previously not associated with species barriers and demonstrate that amino acid residue alterations at positions known to have an impact on the susceptibility of sheep to sheep scrapie also drastically influence PrPsc formation by mouse-adapted scrapie strain 22L. Furthermore, certain residues located on the outer surfaces of helix 2 and 3 in PrPc critically affect conversion to PrPsc, while residues pointing inwards do not. These results have mechanistic relevance, as they comply with the predicted structure of PrPsc multimers and suggest that amino acid residues protruding from the second and third helix might critically affect inter-/or intramolecular stacking of PrPsc molecules.
AD R. Rost, L. Gädtke, E. Maas, H. Schätzl, I. Vorberg, Technical University of Munich, Institute of Virology, Germany; M.H. Groschup, Friedrich-Löffler-Institute, Inst. for Novel and Emerging Infectious Diseases, Germany
SP englisch
PO Schottland