NR AVPG
AU Nishina,K.A.; Deleault,N.R.; Mahal,S.P.; Baskakov,I.V.; Lührs,T.; Riek,R.; Supattapone,S.
TI The stoichiometry of host PrPc glycoforms modulates the efficiency of PrPsc formation in vitro
QU Biochemistry 2006 Nov 28; 45(47): 14129-39
PT journal article; research support, n.i.h., extramural; research support, non-u.s. gov't; research support, u.s. gov't, non-p.h.s.
AB A central event in the formation of infectious prions is the conformational change of a host-encoded glycoprotein, PrPc, into a pathogenic isoform, PrPsc. However, the molecular requirements for efficient PrP conversion remain unknown. In this study, we employed the recently developed protein misfolding cyclic amplification (PMCA) and scrapie cell assay (SCA) techniques to study the role of N-linked glycosylation on prion formation in vitro. The results show that unglycosylated PrPc molecules are required to propagate mouse RML prions, whereas diglycosylated PrPc molecules are required to propagate hamster Sc237 prions. Furthermore, the formation of Sc237 prions is inhibited by substoichiometric levels of hamster unglycosylated PrPc molecules. Thus, interactions between different PrPc glycoforms appear to control the efficiency of prion formation in a species-specific manner.
IN Die Autoren meinen gezeigt zu haben, dass für das Wachstum bestimmter Prionstämme bestimmte Glykosilierungsgrade des normalen zellulären Prionproteins erforderlich sind und das das Wachstum bestimmter Prionstämme durch bestimmte Glykosilierungsstufen inhibiert werden kann.
MH Animals; Blotting, Western; Electrophoresis, Polyacrylamide Gel; Glycosylation; Mice; PrPc Proteins/*metabolism; PrPsc Proteins/*biosynthesis
AD Koren A. Nishina, Nathan R. Deleault, Surachai Supattapone (supattapone@dartmouth.edu), Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755; Sukhvir P. Mahal, Department of Infectology, Scripps Florida, 5353 Parkside Drive, Jupiter, Florida 33458, USA; Ilia Baskakov, Medical Biotechnology Center, University of Maryland, Biotechnology Institute, Baltimore, Maryland 21201, USA; Thorsten Luhrs, Roland Riek,?The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
SP englisch
PO USA