title: Glycosylation differences between the normal and pathogenic prion protein isoforms.
abstract: Prion protein consists of an ensemble of glycosylated variants or glycoforms. The enzymes that direct oligosaccharide processing, and hence control the glycan profile for any given glycoprotein, are often exquisitely sensitive to other events taking place within the cell in which the glycoprotein is expressed. Alterations in the populations of sugars attached to proteins can reflect changes caused, for example, by developmental processes or by disease. Here we report that normal (PrP(C)) and pathogenic (PrP(Sc)) prion proteins (PrP) from Syrian hamsters contain the same set of at least 52 bi-, tri-, and tetraantennary N-linked oligosaccharides, although the relative proportions of individual glycans differ. This conservation of structure suggests that the conversion of PrP(C) into PrP(Sc) is not confined to a subset of PrPs that contain specific sugars. Compared with PrP(C), PrP(Sc) contains decreased levels of glycans with bisecting GlcNAc residues and increased levels of tri- and tetraantennary sugars. This change is consistent with a decrease in the activity of N-acetylglucosaminyltransferase III (GnTIII) toward PrP(C) in cells where PrP(Sc) is formed and argues that, in at least some cells forming PrP(Sc), the glycosylation machinery has been perturbed. The reduction in GnTIII activity is intriguing both with respect to the pathogenesis of the prion disease and the replication pathway for prions.
authors.affiliation: Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom.
authors.forename: P M
authors.initials: PM
authors.lastname: Rudd
authors.forename: T
authors.initials: T
authors.lastname: Endo
authors.forename: C
authors.initials: C
authors.lastname: Colominas
authors.forename: D
authors.initials: D
authors.lastname: Groth
authors.forename: S F
authors.initials: SF
authors.lastname: Wheeler
authors.forename: D J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: M R
authors.initials: MR
authors.lastname: Wormald
authors.forename: H
authors.initials: H
authors.lastname: Serban
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: A
authors.initials: A
authors.lastname: Kobata
authors.forename: R A
authors.initials: RA
authors.lastname: Dwek
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D006031:Glycosylation; D008647:Mesocricetus; D008958:Models, Molecular; D018622:PrP 27-30 Protein / Q000302:isolation & purification / Q000378:metabolism*; D020033:Protein Isoforms / Q000302:isolation & purification / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D020033:Protein Isoforms; D018622:PrP 27-30 Protein