title: The stoichiometry of host PrPC glycoforms modulates the efficiency of PrPSc formation in vitro.
abstract: 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.
authors.affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
authors.forename: Koren A
authors.initials: KA
authors.lastname: Nishina
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Deleault
authors.forename: Sukhvir P
authors.initials: SP
authors.lastname: Mahal
authors.forename: Ilia
authors.initials: I
authors.lastname: Baskakov
authors.forename: Thorsten
authors.initials: T
authors.lastname: Luhrs
authors.forename: Roland
authors.initials: R
authors.lastname: Riek
authors.forename: Surachai
authors.initials: S
authors.lastname: Supattapone
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D051379:Mice; D018621:PrPC Proteins / Q000378:metabolism*; D018620:PrPSc Proteins / Q000096:biosynthesis*
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins