NR ASXD
AU Khalili-Shirazi,A.; Summers,L.; Linehan,J.; Mallinson,G.; Anstee,D.J.; Hawke,S.; Jackson,G.S.; Collinge,J.
TI PrP glycoforms are associated in a strain-specific ratio in native PrPsc
QU Journal of General Virology 2005 Sep; 86(9): 2635-44
PT journal article
AB Prion diseases involve conversion of host-encoded cellular prion protein (PrPc) to a disease-related isoform (PrPsc). Using recombinant human beta-PrP, a panel of monoclonal antibodies was produced that efficiently immunoprecipitated native PrPsc and recognized epitopes between residues 93-105, indicating for the first time that this region is exposed in both human vCJD and mouse RML prions. In contrast, monoclonal antibodies raised to human alpha-PrP were more efficient in immunoprecipitating PrPc than PrPsc, and some of them could also distinguish between different PrP glycoforms. Using these monoclonal antibodies, the physical association of PrP glycoforms was studied in normal brain and in the brains of humans and mice with prion disease. It was shown that while PrPc glycoforms can be selectively immunoprecipitated, the differentially glycosylated molecules of native PrPsc are closely associated and always immunoprecipitate together. Furthermore, the ratio of glycoforms comprising immunoprecipitated native PrPsc from diverse prion strains was similar to those observed on denaturing Western blots. These studies are consistent with the view that the proportion of each glycoform incorporated into PrPsc is probably controlled in a strain-specific manner and that each PrPsc particle contains a mixture of glycoforms.
IN Die PrPsc-Aggregate enthalten die unterschiedlich glykosylierten Formen des PrPsc ungefähr in dem Verhältnis, welches man im Western blot sieht.
MH Animals; Antibodies, Monoclonal/*immunology; Creutzfeldt-Jakob Syndrome/immunology/metabolism; Epitope Mapping; Glycosylation; Humans; Immunohistochemistry; Immunoprecipitation; Mice; PrPc Proteins/immunology; PrPsc Proteins/chemistry/*immunology; Prion Diseases/*immunology/metabolism; Prions/*immunology; Protein Isoforms/*immunology; Recombinant Proteins/immunology; Research Support, Non-U.S. Gov't; Scrapie/immunology/metabolism
AD MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
SP englisch
PO England